Vivek R. Sharma

Randomized controlled trial of irinotecan drug‐eluting beads with simultaneous FOLFOX and bevacizumab for patients with unresectable colorectal liver‐limited metastasis

Reports have demonstrated the superior activity of combining both irinotecan and oxaliplatin (FOLFOXIRI) therapy. An option for gaining similar benefits with less toxicity would be the administration of irinotecan through a hepatic artery approach. The aim of this study was to assess the response and adverse event rates for irinotecan drug‐eluting beads (DEBIRI) with folinic acid, 5‐fluorouracil, and oxaliplatin (FOLFOX) and bevacizumab as a first‐line treatment for unresectable colorectal liver metastasis.

A novel view of paroxysmal nocturnal hemoglobinuria pathogenesis: more motile PNH hematopoietic stem/progenitor cells displace normal HSPCs from their niches in bone marrow due to defective adhesion, enhanced migration and mobilization in response to erythrocyte-released sphingosine-1 phosphate gradient

A novel view of paroxysmal nocturnal hemoglobinuria pathogenesis: more motile PNH hematopoietic stem/progenitor cells displace normal HSPCs from their niches in bone marrow due to defective adhesion, enhanced migration and mobilization in response to erythrocyte-released sphingosine-1 phosphate gradient

Anti-Tumor Monoclonal Antibodies in Conjunction with β-Glucans: A Novel Anti- Cancer Immunotherapy

Monoclonal antibodies (mAbs) have greatly advanced the field of anti-cancer immunotherapy and have made a major impact in clinical medicine. While more mAbs have been approved by the FDA and entered into the clinical therapeutic arena with indications to treat various solid tumors and hematologic malignancies, extensive efforts have also been made to make mAb therapy more effective. Combination therapy of anti-tumor mAbs with chemotherapeutic drugs has been widely used in the clinical patient care. In addition, many immune stimulating agents have been specifically studied for this very purpose. One compound in particular, β-glucan, has shown very promising and exciting results in pre-clinical animal models and early phase human clinical trials. β-Glucans are naturally occurring, abundant polysaccharides with different structures that can be extracted and purified from fungi, bacteria, oats and barley. The active components of yeast-derived β-glucan exert their unique immune stimulating functions by binding specifically to complement receptor 3 (CR3) via lectin-like domain (LLD) and activating CR3 to promote cellular cytotoxicity of iC3b-coated cancer cells. In addition, particulate yeast-derived β-glucan stimulates both innate and adaptive anti-tumor immune responses. This review covers the anti-cancer mechanisms of anti-tumor mAbs and β-glucans, the pre-clinical studies done with β-glucans in conjunction with anti-tumor mAbs in human carcinoma xenograft models, and the preliminary results of human clinical trials with different β-glucans, as well as those of phase I/II and III studies using the combination of yeast-derived soluble β-glucan and anti-tumor mAbs.

Near Real-time Immuno-optical Sensor for Diagnosing Single Point Mutation (A model System: Sensor for Factor V Leiden Diagnosis)

Factor V leiden (FVL) is an abnormality of factor V (FV), a blood coagulation factor. It is a hereditary blood coagulation disorder with a high frequency (3-7% of general population). The most common type of FVL is caused by a single amino acid mutation and, therefore, its diagnosis is currently done only by DNA analysis, which takes a long time and is expensive. We have developed a rapid, accurate, and cost-effective, sandwich immuno-optical sensing method. To produce monoclonal antibodies against FV or FVL, having minimal cross-reactivity with the other molecule, a 20 amino acid sequence (20-mer) of FV or FVL at around the mutation site was utilized. The antibodies were screened first with the 20-mers and then the ones showing no cross-affinity were reacted with native FV or FVL molecules and they showed some cross-reactivity. Using two antibodies having strongest affinity to either FV or FVL molecule, a FV and a FVL preferred sensors, were produced. After verifying that the levels of the antibody affinity to the two different molecules remained constant with changes in analyte concentration, a two-sensor system is developed to quantify FV and FVL in plasma samples. The system quantified the levels of FV and FVL at the maximum error of 0.5 microg/ml-plasma, in their physiological concentration range of 0-12 microg/ml-plasma. The levels of both molecules may provide us whether the patient has FVL or not but also the seriousness level of the disease (homozygous and different level of heterozygous).

Solitary Plasmacytoma in the Setting of Langerhans Cell Histiocytosis

Abstract Langerhans cell histiocytosis (LCH) is an intriguing disorder characterized by the accumulation of specialized dendritic cells called Langerhans cells in several diverse tissues and body sites. It has been cited in numerous case reports to be associated with a wide variety of malignant neoplasms. Although many hypotheses have been suggested, the basis for such associations remains essentially unknown. We describe another association here that to our knowledge has not been reported thus far: a solitary plasmacytoma occurring at a site of previous involvement by LCH. This constitutes a new addition to the now fairly lengthy list of malignant neoplasms that have been reported to occur in the setting of LCH. The possible reasons for such an association are discussed along with a brief review of LCH.

A combination of bortezomib and rituximab yields a dramatic response in a woman with highly refractory immune thrombocytopenic purpura: a case report

IntroductionChronic refractory immune thrombocytopenic purpura can be a challenging condition to treat. By definition, the standard first and second line treatments have failed in these patients and modalities such as thrombopoiesis-stimulating agents and more intensive immunosuppressive drugs are therefore used. However, there still remains a subset of patients who continue to be refractory to treatment.Case presentationWe present the case of a 30-year-old Hispanic woman with recurrent intracranial bleeds, in whom multiple lines of treatment had failed. She was treated with a combination of bortezomib and rituximab based on previously published data that suggested this therapy effectively blocks all antibody-producing cells. Our patient’s platelet counts rapidly improved and subsequently normalized following this treatment.ConclusionTo the best of our knowledge, this case represents the first report of the effective use of bortezomib and rituximab in highly refractory immune thrombocytopenic purpura. We believe further study of this therapy is warranted in this setting.

Survival after Yttrium-90 radioembolization in elderly and nonelderly patients with hepatocellular carcinoma or colorectal cancer liver metastases.

449 Background: Systemic treatment of unresectable hepatocellular carcinoma (HCC) or colorectal cancer liver metastases (CLM) in the elderly can be complicated by increased toxicity. In addition, the increasing incidence of comorbidities with age may preclude surgical resection with curative intent. Hepatic arterial therapy is increasingly utilized in patients with HCC or CLM not amenable to surgical resection. Studies of transarterial chemoembolization in the elderly have generally shown similar safety and efficacy as compared to younger patients, although some studies suggest worse outcomes. The selective nature of radioembolization has the potential for improved tolerability in this patient population. Methods: We report the results of a retrospective review of patients with unresectable HCC or metastatic disease to the liver treated with Yttrium-90 radioembolization at a single institution. Results: Patients were referred for treatment after multidisciplinary evaluation, but were not treated as part o...