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author:("shaver, K A")
1.  HER2-positive advanced breast cancer: optimizing patient outcomes and opportunities for drug development 
British Journal of Cancer  2014;111(10):1888-1898.
Effective targeting of the human epidermal growth factor receptor 2 (HER2) has changed the natural history of HER2 overexpressing (HER2+) metastatic breast cancer. The initial success of trastuzumab improving time to progression and survival rates led to the clinical development of pertuzumab, ado-trastuzumab emtansine and lapatinib. These biologic therapies represent significant additions to the breast medical oncology armamentarium. However, drug resistance ultimately develops and most tumours progress within 1 year. Ongoing studies are evaluating novel therapeutic approaches to overcome primary and secondary drug resistance in tumours, including inhibition of PI3K/TOR, HSP90, IGF-IR and angiogenesis. Mounting experimental data support the clinical testing of immune checkpoint modulators and vaccines. The central nervous system remains a sanctuary site for HER2+ breast cancer and further studies are needed for the prevention and treatment of brain metastases in this population. Despite efforts to identify predictors of preferential benefit from HER2-targeted therapies (e.g., truncated HER2, PTEN loss and SRC activation), HER2 protein overexpression and/or gene amplification remains the most important predictive factor of response to HER2-targeted therapies. In this article, we review the optimal sequence of HER2-targeted therapies and describe ongoing efforts to improve the outcome of HER2+ advanced breast cancer through rational drug development.
PMCID: PMC4229628  PMID: 25025958
Erbb-2; trastuzumab; pertuzumab; trastuzumab-DM1; lapatinib; breast neoplasm
2.  Intravenous albumin infusion is an effective therapy for hyponatremia in patient with malignant ascites 
Indian Journal of Nephrology  2014;24(1):51-53.
There are few reports about the treatment of moderate to severe hyponatremia associated with malignant liver metastasis. Here, we report using intravenous salt poor albumin infusion to treat hypervolemic cirrhosis related hyponatremia. A 58-year-old female with ascites secondary to metastatic breast cancer was referred to our department with symptomatic hyponatremia (serum sodium concentration of 121 mEq/L). The serum sodium level was corrected slowly over 2 days with intravenous albumin infusion and the patient's symptoms – fatigue, nausea, dizziness and headache improved.
PMCID: PMC3927194  PMID: 24574634
Albumin infusion; cirrhosis; hypervolemic hyponatremia; hyponatremia; salt poor albumin
3.  Elevated human chorionic gonadotropin levels in patients with chronic kidney disease: Case series and review of literature 
Indian Journal of Nephrology  2013;23(6):424-427.
Women are often subjected to serum human chorionic gonadotropin (HCG) testing prior to diagnostic and therapeutic interventions. A positive result leads to further testing to rule out pregnancy and avoid possible fetal teratogenicity. The impact of chronic kidney disease (CKD) on HCG testing has not been studied. We report a series of 5 women out of 62 with CKD, who had a positive HCG test on routine pre-transplant screening at a single transplant center. We analyzed their case records retrospectively. Despite aggressive investigation, their elevated HCG levels remained unexplained. The positive test contributed to delays in transplantation and increased overall cost of treatment.
PMCID: PMC3841510  PMID: 24339520
Human chorionic gonadotropin; kidney disease; transplantation
4.  The role of p21-activated kinase in the initiation of atherosclerosis 
p21-activated kinase (PAK) has been implicated in the inflammatory activation of endothelial cells by disturbed fluid shear stress, which is the initiating stimulus in atherosclerosis. The study addresses whether PAK1 contributes to inflammatory marker expression in endothelial cells at atherosclerosis-susceptible regions of arteries in vivo.
Aortas from WT and PAK1-/- C57BL/6J mice on a normal chow diet were fixed, dissected and processed for immunohistochemistry using a panel of inflammatory markers. We visualized and quantified staining in the endothelium at the greater and lesser curvatures of the arch of aorta, as atherosclerosis-resistant and susceptible regions, respectively.
Fibronectin, VCAM-1 and the activated RelA NF-κB subunit were localized to the lesser curvature and decreased in PAK1-/- mice. The activated RelB NF-κB subunit was also localized to the lesser curvature but was increased in PAK1-/- mice. Low levels of staining for ICAM-1 and the monocyte/macrophage marker Mac2 indicated that overall inflammation in this tissue was minimal.
These data show that PAK1 has a significant pro-inflammatory function at atherosclerosis-prone sites in vivo. These effects are seen in young mice with very low levels of inflammation, suggesting that inflammatory activation of the endothelium is primarily biomechanical. Activation involves NF-κB, expression of leukocyte recruitment receptors and fibronectin deposition. These results support and extend in vitro studies demonstrating that PAK contributes to activation of inflammatory pathways in endothelial cells by fluid shear stress.
PMCID: PMC3489605  PMID: 22824149
Fluid shear stress; Endothelial cells; Vascular inflammation; Fibronectin
5.  Eastern Canadian Colorectal Cancer Consensus Conference: application of new modalities of staging and treatment of gastrointestinal cancers 
Current Oncology  2012;19(3):169-174.
The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Ottawa, Ontario, October 22–23, 2010. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer, such as the use of epidermal growth factor inhibitors in metastatic colon cancer, the benefit of calcium and magnesium with oxaliplatin chemotherapy, the role of microsatellites in treatment decisions for stage ii colon cancer, the staging and treatment of rectal cancer, and the management of colorectal and metastatic pancreatic cancers.
PMCID: PMC3364767  PMID: 22670096
Consensus guideline; colorectal cancer; rectal cancer; pancreatic cancer; microsatellites; egfri
6.  Blogging during IPNA meeting: Reaching out to fellows at home 
Indian Journal of Nephrology  2012;22(2):148-149.
PMCID: PMC3391818  PMID: 22787323
7.  Podocyturia: Is there any clinical utility? 
Indian Journal of Nephrology  2011;21(4):219-220.
PMCID: PMC3193661  PMID: 22022078

Results 1-7 (7)