Window of opportunity treatment in breast cancer

Window of opportunity therapies, which involve short‐term administration of systemic therapy between cancer diagnosis and surgery, have raised significant interest in recent years as a mean of assessing the sensitivity of a patient's cancer to therapy prior to surgery. There is now compelling evidence that in patients with early stage hormone‐receptor positive breast cancer, a 2‐week preoperative treatment with standard hormone therapies in a preoperative window period provides important prognostic information, which in turn helps to aid decision‐making regarding treatment options. Changes in short‐term biomarker endpoints such as cell proliferation measured by Ki‐67 can act as surrogate markers of long‐term outcomes. Paired tissues obtained pre‐ and post‐investigational treatment, without having to subject the patient to additional biopsies, can then be used to conduct translational research to investigate predictive biomarkers and pharmacodynamics. In this review, we will examine the utility and challenges of window of opportunities therapies in breast cancer in the current literature, and the current Australian and international trial landscape in this clinical space.     

Osteopontin is an initial mediator of inflammation and liver injury during obstructive cholestasis after bile duct ligation in mice

Osteopontin (OPN) is a chemotactic factor which can be cleaved to the pro-inflammatory form by matrix metalloproteinases (MMPs). To test the hypothesis that OPN can modulate inflammatory liver injury during cholestasis, wild-type (WT) C57BL/6 and OPN knockout (OPN-KO) mice underwent bile duct ligation (BDL). OPN-KO mice showed significant reduction in liver injury (plasma ALT and necrosis) and neutrophil recruitment compared with WT animals at 24 h but not 72 h after BDL. In WT mice, a 4-fold increase in hepatic MMP-3 mRNA and elevated MMP activities and cleaved OPN levels were observed in bile. WT mice subjected to BDL in the presence of the MMP inhibitor BB-94 showed reduced liver injury, less neutrophil extravasation and diminished levels of cleaved OPN in bile. Thus, during obstructive cholestasis, OPN released from biliary epithelial cells could be cleaved by MMPs in bile. When the biliary system leaks, cleaved OPN enters the parenchyma and attracts neutrophils. In the absence of OPN, other chemoattractants, e.g. chemokines, mediate a delayed inflammatory response and injury. Taken together, our data suggest that OPN is the pro-inflammatory mediator that initiates the early neutrophil-mediated injury phase during obstructive cholestasis in mice.     

Drug-induced acute pancreatitis: A rare manifestation of an incomplete “dapsone syndrome”

Drug-induced acute pancreatitis (AP) is under-reported, and a large number of drugs are listed as offenders, but are often overlooked. Knowledge about the possible association of medications in causing AP is important, and needs a high index of suspicion, especially with drugs that have been reported to be the etiology only rarely. Dapsone, a commonly used drug, can cause various hypersensitivity reactions including AP collectively called “dapsone syndrome.” Here, we report dapsone-induced AP in a young man. Our case shows certain dissimilarities like associated acute renal failure and acute hemolysis not previously described.KEY WORDS: Acute pancreatitis, acute renal failure, adverse drug reactions, dapsone syndrome, drug-induced pancreatitis     

Hepatocellular carcinoma (HCC) versus non-HCC: accuracy and reliability of Liver Imaging Reporting and Data System v2018

Abdominal Radiology - The Liver Imaging Reporting and Data System (LI-RADS) was created to standardize the diagnostic criteria for hepatocellular carcinoma (HCC) and has undergone multiple...     

Foliar Application of Seaweed Sap Enhances Growth,Yield and Quality of Maize in Eastern Himalayas

Maize (Zea mays L.) productivity in hilly regions of North Eastern Region (NER) of India is very low due to limited use of manures and fertilizers. Under such situation, seaweed sap can become an alternative as it is an organic bio-stimulant. Experiment with extracts from marine algae Kappaphycus alvarezii (K sap) and Gracilaria edulis (G sap) was conducted during 2012 and 2013 to assess the efficacy of seaweed saps on growth, productivity and quality of maize and their role in economizing the chemical fertilizer requirement. Results revealed that K or G sap @ 10% and above concentrations along with 100% recommended dose of fertilizer (RDF) recorded significantly higher plant height, dry matter, chlorophyll content, yield attributes and yield of maize compared to control (water spray). The nitrogen (N) and protein content in grain was the highest under 15% K sap + 100% RDF followed by 15% G sap + 100% RDF. Application of K or G sap at 10% concentrations + 100% RDF also significantly increased micronutrient (copper, zinc, manganese and iron) concentrations in maize grains. The available nitrogen, phosphorous and potassium content in soil was recorded to be lowest under 7.5% K sap + 50% RDF. Thus, foliar application of 10% K or G sap along with 100% RDF is recommended for sustainable maize production in NER of India and other ecosystems elsewhere.

     

Chronic Administration of Bacopa Monniera Increases BDNF Protein and mRNA Expressions: A Study in Chronic Unpredictable Stress Induced Animal Model of Depression

Objective

The present study aimed to investigate whether graded doses of Bacopa Monniera (BM) extract could produce antidepressant-like effects in chronic unpredictable stress (CUS) induced depression in rats and its possible mechanism(s).

Methods

Rats were subjected to an experimental setting of CUS. The effect of BM extract treatment in CUS-induced depression was examined using behavioral tests including the sucrose consumption, open field test and shuttle box escape test. The mechanism underlying the antidepressant-like action of BM extract was examined by measuring brain-derived neurotrophic factor (BDNF) protein and mRNA expression in brain tissues of CUS-exposed rats.

Results

Exposure to CUS for 4 weeks caused depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity and escape latency. In addition, it was found that BDNF protein and mRNA levels in the hippocampus and frontal cortex were lower in CUS-treated rats, as compared to controls. Daily administration of the graded doses of BM extract during the 4-week period of CUS significantly suppressed behavioral changes and attenuated the CUS-induced decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex.

Conclusion

The results suggest that BM extract alleviates depression induced by CUS. Present study also confirms that 80-120 mg/kg doses of BM extract have significantly higher antidepressant-like activity.     

Application of Digital Image Correlation in Space and Frequency Domains to Deformation Analysis of Polymer Film

Using speckle patterns formed by an expanded and collimated He-Ne laser beam, we apply DIC (Digital Image Correlation) methods to estimate the deformation of LLDPE (linear low-density polyethylene) film. The laser beam was transmitted through the film specimen while a tensile machine applied a load to the specimen vertically. The transmitted laser light was projected on a screen, and the resultant image was captured by a digital camera. The captured image was analyzed both in space and frequency domains. For the space-domain analysis, the random speckle pattern was used to register the local displacement due to the deformation. For the frequency-domain analysis, the diffraction-like pattern, due to the horizontally-running, periodic groove-like structure of the film was used to characterize the overall deformation along vertical columns of analysis. It has been found that when the deformation is small and uniform, the conventional space domain analysis is applicable to the entire film specimen. However, once the deformation loses the spatial uniformity, the space-domain analysis falls short if applied to the entire specimen. The application of DIC to local (windowed) regions is still useful but time consuming. In the non-uniform situation, the frequency-domain analysis is found capable of revealing average deformation along each column of analysis.