Albumin Based Iohexol Nanoparticles for Computed Tomography: An In Vivo Study

Iohexol is a commonly used second generation non-ionic iodinated contrast agent with a multitude of advantages such as low osmolarity and competent intravenous countenance having minimum adverse reactions. Our study anticipated to improve the efficacy of Iohexol as a contrast enhancing agent for Computed Tomography, by envisaging bio-compatible albumin based Iohexol nanoparticles. This nanoparticulate system was developed primarily to enhance the anatomic imaging while increasing its residence time in the blood pool. Towards this goal, we developed Iohexol albumin nanoparticles using glutaraldehyde as a cross linking agent, and Polyethylene glyocol Iohexol albumin nanoparticles by physical adsorption to ameliorate its circulation time. These formulations were studied in comparison to the clinically available Iopamidol™. Both Iohexol albumin nanoparticles and Polyethylene glyocol Iohexol albumin nanoparticles were characterized for its size, physicochemical properties and entrapment efficiency. Iohexol albumin nanoparticles showed a size range of 254±5 nm and post surface modification the size of Polyethylene glyocol Iohexol albumin nanoparticles was found to be 283±7 nm in diameter, with and entrapment efficiency Iohexol as of 85%. Further, In vivo computed tomography imaging in New Zealand white rabbits for the developed formulations manifested an enhancement in the anatomical structures of heart, liver and kidneys along with an increased residence time in the blood pool of 3 h in contrast to Iopamidol™. Our study interprets that Polyethylene glyocol Iohexol albumin nanoparticles have prolonged residence time producing much greater conspicuity of anatomic features and warrants further detail study of the formulation in disease models

In vitro antimitotic activity and in silico study of some 6-fluoro-triazolo-benzothiazole analogues

In this work, nine 6-fluoro-triazolo-benzothiazole derivatives were prepared and evaluated for in vitro antimitotic activity. In addition, in silico study was also done using tubulin protein (PDB: 6QQN) by molecular docking method. Results revealed that TZ2 and TZ9 were the most active compounds with antimitotic action opposing the standard drug, aspirin. Results of molecular docking exhibited the inhibitory potential of triazolo-benzothiazole against tubulin protein. The mitotic study indicates the efficacy of triazolo-benzothiazole analogues in inhibiting the proliferation of cancer cells either by promoting microtubule formation or affecting microtubules, thereby preventing microtubule breakdown

Re-establishing Responsiveness in a Case of Refractory Metastatic Rectal Cancer with a Personalized de novo Combination Regimen

Introduction: Encyclopedic Tumor Analysis (ETA) is multi-analyte, molecular and functional interrogation to identify latent vulnerabilities in solid tumors which can then be targeted in organ- and label-agnostic combination treatment regimens.Case Presentation: We describe here a case of metastatic rectal cancer in a 61-year-old male who was progressed on all prior Standard of Care (SoC) treatment modalities including surgery, chemotherapy and radiotherapy. We addressed disease recurrence via personalized therapy guided by ETA which revealed characteristic molecular heterogeneity in primary and metastatic lesions in terms of single nucleotide variations (SNVs) and gene copy number variations (CNVs).  Notably, a novel TBL1XR1 (Exon1) – PIK3CA (Exon 2) gene fusion was identified in the tumor along with gene copy number gains in TERT, IGF-1R, MYC, FGFR1 and EGFR genes.Conclusion: ETA based molecular analysis with synchronous in vitro chemo-sensitivity profiling strategy helped to define de novo combinatorial therapy regimen of targeted and cytotoxic drugs which countered disease progression at each instance and led to the durable regression of primary as well as metastatic lesions

Spectrum of pediatric skin biopsies

Background: Skin diseases are common in childhood and they are common reasons for pediatric visits to the hospital. In spite of this high occurrence, there are very few prospective studies addressing this issue. Aims: The present study was directed at determining the spectrum of dermato-pathological lesions encountered in a large general tertiary care hospital, over a two-year period. Materials and Methods: 107 cases formed the total sample studied, in a part prospective and part retrospective study. A detailed clinical history was recorded on a proforma prepared for the purpose and gross photographs were taken wherever possible. Results: Skin biopsies accounted for 7.29% of the total surgical pathology load, 55.44% of the total pediatric biopsies and 10.82% of the total number of skin biopsies. The age and sex distribution pattern revealed that the maximum number of biopsies (62.61%) were of older children, with a male preponderance (57.94%). The anatomic distribution pattern indicated predominant involvement of the limbs (59.82%). The maximum numbers of cases were of infectious nature (24.29%); the most frequently encountered being borderline tuberculoid Hansen′s disease (8.4%). A positive correlation with the clinical diagnosis was obtained in 56.07% cases. Conclusions: Histopathology contributed to the diagnosis in a significant number of (82.23%) cases, indicating its importance and utility

Accurate prostate cancer detection based on enrichment and characterization of prostate cancer specific circulating tumor cells

Abstract Background The low specificity of serum PSA resulting in the inability to effectively differentiate prostate cancer from benign prostate conditions is a persistent clinical challenge. The low sensitivity of serum PSA results in false negatives and can miss high‐grade prostate cancers. We describe a non‐invasive test for detection of prostate cancer based on functional enrichment of prostate adenocarcinoma associated circulating tumor cells (PrAD‐CTCs) from blood samples followed by their identification by immunostaining for pan‐cytokeratins (PanCK), prostate specific membrane antigen (PSMA), alpha methyl‐acyl coenzyme‐A racemase (AMACR), epithelial cell adhesion molecule (EpCAM), and common leucocyte antigen (CD45). Methods Analytical validation studies were performed to establish the performance characteristics of the test using VCaP prostate cancer cells spiked into healthy donor blood (HDB). The clinical performance characteristics of the test were evaluated in a case–control study with 160 known prostate cancer cases and 800 healthy males, followed by a prospective clinical study of 210 suspected cases of prostate cancer. Results Analytical validation established analyte stability as well as acceptable performance characteristics. The test showed 100% specificity and 100% sensitivity to differentiate prostate cancer cases from healthy individuals in the case control study and 91.2% sensitivity and 100% specificity to differentiate prostate cancers from benign prostate conditions in the prospective clinical study. Conclusions The test accurately detects PrAD‐CTCs with high sensitivity and specificity irrespective of stage, serum PSA or Gleason score, which translates into low risks of false negatives or overdiagnosis. The high accuracy of the test could offer advantages over PSA based prostate cancer detection