Can we better select patients with metastatic renal cell carcinoma for cytoreductive nephrectomy?

BACKGROUND:

The benefits of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) should outweigh surgical morbidity. Even when the generally agreed upon selection criteria for CN are met, some patients do poorly after surgery. The objective of this study was to identify preoperative factors that were prognostic of outcome in patients who were being considered for CN.

METHODS:

The authors conducted a retrospective study to investigate the overall survival (OS) of patients who underwent CN using the OS of patients with mRCC who did not undergo CN as a referent group. Patients who underwent CN were divided into 2 groups based on when their OS diverged from that of nonsurgical patients. Chi‐square analysis was used to identify variables that differed between the 2 surgical groups. Multivariate Cox proportional hazards regression was used to analyze those variables for the entire CN cohort. Risk factors were defined as preoperative variables that remained significant on multivariate analysis. The median OS and the overall risk of death were calculated based on the number of risk factors.

RESULTS:

From 1991 to 2007, 566 patients who were eligible for or received systemic therapy underwent CN, and 110 patients received medical therapy alone. On multivariate analysis, independent preoperative predictors of inferior OS in surgical patients included a lactate dehydrogenase level greater than the upper limit of normal, an albumin level less than the lower limit of normal, symptoms at presentation caused by a metastatic site, liver metastasis, retroperitoneal adenopathy, supradiaphragmatic adenopathy, and clinical tumor classification ≥T3. Inferior OS and an increased risk of death were correlated positively with the number of risk factors. Surgical patients who had ≥4 risk factors did not appear to benefit from CN.

CONCLUSIONS:

The authors of this report identified 7 preoperative variables that permitted them to identify patients who were unlikely to benefit from CN. Cancer 2010. © 2010 American Cancer Society.     

Use of Blood Smears and Dried Blood Spots for Polymerase Chain Reaction–Based Detection and Quantification of Bacterial Infection and Plasmodium falciparum in Severely Ill Febrile African Children

Molecular approaches offer a means of testing archived samples stored as dried blood spots in settings where standard blood cultures are not possible. Peripheral blood films are one suggested source of material, although the sensitivity of this approach has not been well defined. Thin blood smears and dried blood spots from a severe pediatric malaria study were assessed using specific polymerase chain reaction (PCR) primers to detect non-typhoidal Salmonella (NTS; MisL gene), Streptococcus pneumoniae (lytA), and Plasmodium falciparum (18S rRNA). Of 16 cases of NTS and S. pneumoniae confirmed on blood culture, none were positive by PCR using DNA extracts from blood films or dried blood spots. In contrast, four of 36 dried blood spots and two of 178 plasma samples were PCR positive for S. pneumoniae, despite negative bacterial blood cultures, suggesting false positives. Quantitative assessment revealed that the effective concentration of P. falciparum DNA in blood films was three log orders of magnitude lower than for dried blood spots. The P. falciparum kelch13 gene could not be amplified from blood films. These findings question the value of blood PCR-based approaches for detection of NTS and S. pneumoniae, and show that stored blood films are an inefficient method of studying P. falciparum.     

Scientific evidence for traditional claim of anti-obesity activity of Tecomella undulata bark

Ethnopharmacological relevance

The bark of Tecomella undulata is traditionally claimed in the treatment of various disease ailments including obesity and cancer. Till now there are no studies about anti-obesity activity of Tecomella undulata bark.

Aim of the study

The present study was aimed to establish a scientific evidence for anti-obesity efficiency of ethyl acetate extract of Tecomella undulata bark (EATUB). Further to standardize the active fractions of EATUB using different biomarkers.

Materials and methods

We investigated activity of EATUB fractions (F1–F7) using 3T3-L1 fibroblasts. Further, F1-mediated effects were characterized by determining mRNA and protein levels of SIRT1, one of the key targets for the treatment of obesity, using semi-quantitative RT-PCR (sqRT-PCR) and western blot analysis. The consequences of modulation of SIRT1 on mRNA and protein levels of various adipogenesis mediators like PPARγ, C/EBPα, E2F1, leptin, adiponectin and LPL were also studied. In vivo studies were performed using High Fat Diet (HFD) obese mice.

Results

Our data showed that compared to controls, preadipocytes and adipocytes incubated with F1 exhibited a significant decrease in adipogenesis and lipogenesis. In addition, sqRT-PCR and western blot analysis showed significant increase in SIRT1 and adiponectin levels and decrease in PPARγ, C/EBPα, E2F1, leptin and LPL levels in preadipocytes and adipocytes. In vivo studies of F1 in HFD induced obese mice showed significant improvement in lipid profile and glucose levels. The bioactive fraction (F1) was determined to possess 4.95% of ferulic acid.

Conclusion

Thus, our findings signified the beneficial effects of Tecomella undulata bark in pharmacologic interventions related to obesity and metabolic disorders. Ferulic acid and rutin are being reported and quantified for the first time from the bark of Tecomella undulata.     

Role of mangiferin on biochemical alterations and antioxidant status in isoproterenol-induced myocardial infarction in rats

The current study dealt with the protective role of mangiferin, a polyphenol from Mangifera indica Linn. (Anacardiaceae), on isoproterenol (ISPH)-induced myocardial infarction (MI) in rats through its antioxidative mechanism. Subcutaneous injection of ISPH (200 mg/kg body weight in 1 ml saline) to rats for 2 consecutive days caused myocardial damage in rat heart, which was determined by the increased activity of serum lactate dehydrogenase (LDH) and creatine phosphokinase isoenzymes (CK-MB), increased uric acid level and reduced plasma iron binding capacity. The protective role of mangiferin was analyzed by triphenyl tetrazolium chloride (TTC) test used for macroscopic enzyme mapping assay of the ischemic myocardium. The heart tissue antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase and glutathione reductase activities, non-enzymic antioxidants such as cerruloplasmin, Vitamin C, Vitamin E and glutathione levels were altered in MI rats. Upon pretreatment with mangiferin (100 mg/kg body weight suspended in 2 ml of dimethyl sulphoxide) given intraperitoneally for 28 days to MI rats protected the above-mentioned parameters to fall from the normal levels. Activities of heart tissue enzymic antioxidants and serum non-enzymic antioxidants levels rose significantly upon mangiferin administration as compared to ISPH-induced MI rats. From the present study it is concluded that mangiferin exerts a beneficial effect against ISPH-induced MI due to its antioxidant potential, which regulated the tissues defense system against cardiac damage.     

Antiproliferative activity and standardization of Tecomella undulata bark extract on K562 cells

Ethnopharmacological relevance

The bark of Tecomella undulata is primarily used in the treatment of syphilis, painful swellings and cancer by traditional healers. Also, it is claimed to be useful in treating urinary discharges, enlargement of spleen, leucorrhoea, leukoderma, tumors, liver disorders, gonorrhea, gout and promotes wound healing in Indian traditional system of medicine.

Aim

To establish a scientific validation for the antitumor effects of Tecomella undulata bark and explore the mechanistic pathway in chronic myeloid leukemia cell line, K562. The study was further extended to standardize the extract using quercetin as biomarker.

Methods

Induction of apoptosis by chloroform extract of Tecomella undulata bark (CTUB) was determined by MTT, Annexin V and caspase activation assays. The cell cycle analysis was done by flow cytometer and nuclear staining by DAPI. The standardization of the extract was performed through reverse phase-HPLC method under PDA detection.

Result

Results clearly showed the induction of apoptosis by CTUB in K562 cells. The effect was found to be dose dependent, having IC₅₀ of 30 μg/ml with activation of FAS, FADD, caspase 8, caspase 3/7 and fragmentation of DNA. The bioactive CTUB was determined to possess 0.03% (w/w) of quercetin.

Conclusion

The investigation clearly demonstrated the potential antitumor effect of CTUB, thereby validating the traditional claim. Quercetin, known to have anticancer activity is being reported and quantified for the first time from the bark of Tecomella undulata.     

Altered expression of TGF-β1 and TGF-βR2 in tissue samples compared to blood is associated with food habits and survival in esophageal squamous cell carcinoma

In the transforming growth factor β (TGF-β) signaling pathway, TGF-β1 and TGF-β receptor 2 (TGF-βR2) are essential regulatory components which play an important role in different type of cancer. Expressions of TGF-β1 and TGF-βR2 were done by real-time qPCR in both biopsy and blood samples collected from esophageal squamous cell carcinoma (ESCC) patients (n = 76). The expression profiles were correlated with different lifestyle factors and clinicopathological parameters. Kaplan-Meier survival analysis and Cox regression analysis were performed to estimate survival and hazard outcomes of different parameters. TGF-β1 showed upregulation in 91% tissue samples (2.84 ± 1.34*) and 55% blood samples (2.43 ± 1.24*) whereas expression of TGF-βR2 showed downregulation in 89% tissue samples (0.27 ± 0.23*) and 75% blood samples (0.30 ± 0.26*). Among all the parameters, TGF-β1 expression is significant with histopathology grade, consumption of betel nut and smoked food whereas TGF-βR2 expression is significant only with dysphagia grade in both blood and tissue samples and while analyzing both male and female patients separately. Consuming alcohol and hot food, difference in tumor stage and metastasis were found to have statistically significant (P < 0.05) impact on survival and mortality of male patients while consuming hot food, tobacco, metastasis and TGF-βR2 expression in tissue level were found to associate with survival and mortality of female patients. Expression of both TGF-β1 and TGF-βR2 in tissue samples may be prospective biomarkers for screening of ESCC among the Northeast population. Survival outcomes and hazard analysis supports the importance of some clinicopathological and lifestyle factors on ESCC development, whereas expression study depicts association of change in expression of the studied genes in ESCC patients.*Mean fold change.     

Megakaryocytes,erythropoietic and granulopoietic cells express CAL2 antibody in myeloproliferative neoplasms carrying CALR gene mutations

Testing for the CALR mutation is included in the updated WHO criteria for essential thrombocythaemia (ET) and primary myelofibrosis (PMF). We report on the application of the CAL2 monoclonal antibody, raised against the mutated CALR gene to myeloid cases. The immunostain was used on 116 acute myeloid leukaemias (AML) and 66 myeloproliferative neoplasms (MPN) or myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN). None of AML cases was stained by the CAL2 antibody, while 20/66 MPNs and MDS/MPNs appeared positive. Fourteen of the latter cases were studied by molecular techniques, and all showed aberrations of the CALR gene. In addition, CAL2 positivity was found in some small‐sized elements besides megakaryocytes. By double staining, these elements corresponded to small megakaryocytes as well as both erythroid and myeloid precursors. This finding suggests possible occurrence of CALR gene abnormalities in a stem cell.     

A follow-up study on visual outcome after camp-based intracapsular cataract extraction

The visual outcome of 164 intracapsular cataract extractions (ICCE) performed in 158 patients at an eye-camp was evaluated. 93.3% had a preoperative visual acuity of less than 3/60. On the 4th/5th post-operative day, 39.3% had a visual acuity between 6/18 and 6/36; 84.7% had vision better than 3/60. Six weeks post-operatively, 44.1% had visual acuity better than 6/18 and a total of 84.1% better than 3/60. The vision of 40.7% improved between the 4th/5th post-operative day and the follow-up visit at 6 weeks. 46.4% of patients had post-operative corrected visual acuity better than 6/18, 24.3% had vision between 6/18 and 6/36, and a total of 84.3% had vision better than 3/60. The patients' satisfaction in terms of improvement in mobility and ability to do housework at 6 weeks after the operation correlated better with the improvement in vision in terms of the number of Snellen's lines than with the actual post-operative visual acuity.