Inverse 4D conformal planning for lung SBRT using particle swarm optimization.

A critical aspect of highly potent regimens such as lung stereotactic body radiation therapy (SBRT) is to avoid collateral toxicity while achieving planning target volume (PTV) coverage. In this work, we describe four dimensional conformal radiotherapy using a highly parallelizable swarm intelligence-based stochastic optimization technique. Conventional lung CRT-SBRT uses a 4DCT to create an internal target volume and then, using forward-planning, generates a 3D conformal plan. In contrast, we investigate an inverse-planning strategy that uses 4DCT data to create a 4D conformal plan, which is optimized across the three spatial dimensions (3D) as well as time, as represented by the respiratory phase. The key idea is to use respiratory motion as an additional degree of freedom. We iteratively adjust fluence weights for all beam apertures across all respiratory phases considering OAR sparing, PTV coverage and delivery efficiency. To demonstrate proof-of-concept, five non-small-cell lung cancer SBRT patients were retrospectively studied. The 4D optimized plans achieved PTV coverage comparable to the corresponding clinically delivered plans while showing significantly superior OAR sparing ranging from 26% to 83% for D max heart, 10%-41% for D max esophagus, 31%-68% for D max spinal cord and 7%-32% for V 13 lung.

Pregnancy-associated anaplastic large-cell lymphoma of the breast: a rare mimic of ductal carcinoma.

Anaplastic large-cell lymphoma (ALCL) is a rare T-cell lymphoma typically seen in children and young adults. It has been described in numerous sites; however, the breast is one of the least common locations. We herein report a case of ALCL arising in the breast of a 36-yr-old pregnant woman. To our knowledge this is the second such case in the English literature. We would like to highlight the cytologic and histologic features of ALCL, as this case was initially misdiagnosed as a ductal carcinoma. Differential diagnosis with other tumors is also discussed. This case serves to emphasize the importance of the triple test, and the need for correlation of fine-needle aspiration findings with core biopsy findings in breast tumor management.

Pleomorphic adenoma of the breast: case report and review of the literature.

Pleomorphic adenoma of the breast (PAB) is a very rare neoplasm. Although quite unique in its morphology, PAB shares some similarities with adenomyoepithelioma and is considered by some authors as a variant of this entity. Cytologic diagnosis of this lesion can be very challenging, especially when limited sampling is available. The differential diagnosis of PAB includes metaplastic carcinoma. On cytologic material, fibroadenoma and phyllodes tumor should also be considered within the differential diagnosis. We report the findings in a case of PAB, initially misdiagnosed as mucinous carcinoma on fine-needle aspiration, and review the literature regarding this entity. Correct identification of this benign mammary neoplasm is important to avoid unnecessarily aggressive treatment.

Clinical relevance of molecular markers in lung cancer.

The last two decades have seen an exponential growth of our knowledge on the molecular biology of cellular processes and neoplastic transformation. There is high expectation that these advances will be translated into further improvement in the care of cancer patients, especially in the areas of prevention, diagnosis and treatment. Realizing that the histopathological classification of lung cancer has reached its limit in providing additional critical information to further improve treatment strategy, numerous molecular aberrations occurring in lung cancers have been explored as potential new diagnostic markers and markers for molecular sub-staging. Despite extensive studies, most results remain largely controversial. This manuscript will briefly review molecular/genetic changes that have been investigated as candidate diagnostic, prognostic and predictive markers and as biomarkers for early detection in lung cancer. A more concerted and global approach to study the clinical relevance of molecular changes in lung cancers is required in the future.

Constitutive and growth factor-regulated phosphorylation of caveolin-1 occurs at the same site (Tyr-14) in vivo: identification of a c-Src/Cav-1/Grb7 signaling cassette.

Caveolin-1 was first identified as a phosphoprotein in Rous sarcoma virus (RSV)-transformed chicken embryo fibroblasts. Tyrosine 14 is now thought to be the principal site for recognition by c-Src kinase; however, little is known about this phosphorylation event. Here, we generated a monoclonal antibody (mAb) probe that recognizes only tyrosine 14-phosphorylated caveolin-1. Using this approach, we show that caveolin-1 (Y14) is a specific tyrosine kinase substrate that is constitutively phosphorylated in Src- and Abl-transformed cells and transiently phosphorylated in a regulated fashion during growth factor signaling. We also provide evidence that tyrosine-phosphorylated caveolin-1 is localized at the major sites of tyrosine-kinase signaling, i.e. focal adhesions. By analogy with other signaling events, we hypothesized that caveolin-1 could serve as a docking site for pTyr-binding molecules. In support of this hypothesis, we show that phosphorylation of caveolin-1 on tyrosine 14 confers binding to Grb7 (an SH2-domain containing protein) both in vitro and in vivo. Furthermore, we demonstrate that binding of Grb7 to tyrosine 14-phosphorylated caveolin-1 functionally augments anchorage-independent growth and epidermal growth factor (EGF)-stimulated cell migration. We discuss the possible implications of our findings in the context of signal transduction.

Ribosome-initiator tRNA complex as an intermediate in translation initiation in Escherichia coli revealed by use of mutant initiator tRNAs and specialized ribosomes.

For functional studies of mutant Escherichia coli initiator tRNAs in vivo, we previously described a strategy based on the use of tRNA genes carrying an anticodon sequence change from CAU to CUA along with a mutant chloramphenicol acetyltransferase (CAT) gene carrying an initiation codon change from AUG to UAG. Surprisingly, under conditions where the mutant initiator tRNA is optimally active, the CAT gene with the UAG initiation codon produced more CAT protein (3- to 9-fold more depending on the conditions) than the wild-type CAT gene. Here we show that two new mutant CAT genes having GUC and AUC initiation codons also produce more of the CAT protein in the presence of the corresponding mutant initiator tRNAs. These results are most easily understood if assembly of the 30S ribosome-initiator tRNA-mRNA initiation complex in vivo proceeds with the 30S ribosome binding first to the initiator tRNA and then to the mRNA. In cells overproducing the mutant initiator tRNAs, most ribosomes would carry the mutant initiator tRNA and these ribosomes would select the mutant CAT mRNA over the other mRNAs.

Jaundice secondary to spilled gallstone during laparoscopic cholecystectomy.

Advantages of.laparoscopiC cholecystectomy (LC) in terms of shorter hospital stay, less pain, and diminished disabilrty are well documented. Less well documented are the long-term comptications of this procedure. We report a patient who developed obstructive jaundice 8 months following LC from a spilled gallstone. In our review of the literature using MEDLINE from January 1990to June 1995,we did not find this complication reported.

A study of inventory analysis in Forward Medical Stores Depot.

A study was conducted in Forward Medical Stores Depot with a view to determine the scope of its utility, efficacy and to educate staff working in the depot regarding techniques of inventory analysis system. 292 drugs were selected and were studied for one year from 01 Apr 91 to 31 Mar 92. The expenditure on 01 section (drugs) without application of inventory analysis during 90-91 was Rs. 60, 82,926.70. The expenditure was Rs. 51,61,589.08 after application of the techniques. A significant statistical reduction in the consumption pattern and expenditure was noticed by Rs. 9,21,3773.62. An uninterrupted supply of vital and essential drugs was ensured upto great extent.