Objective. To develop a genotype exercise to improve pharmacy students' comprehension of pharmacogenetic principles that apply to patient care. Design. Deoxyribonucleic acid (DNA) was collected during class from 10 student volunteers and subjected to genotype analysis. The results were presented to the class and discussed in the context of a patient genetic counseling session. Students completed a survey instrument regarding their attitudes toward this learning experience. Assessment. Students indicated that the exercise engaged them with the course content and would positively influence their ability to apply pharmacogenetic principles to patient care.Conclusion. An applied genotype exercise enhanced learning of pharmacogenetic principles. Based on these findings, conducting a genotype exercise in a large classroom setting is feasible in terms of time and expense, and meaningful in terms of student satisfaction.

This study demonstrates the potential of combining computational and in vitro approaches to determine the affinity of compounds for hPEPT1 and, in turn, provides insights into key molecular interactions with this transporter.

Mantle cell lymphoma (MCL) is a distinct histologic subtype of B cell non-Hodgkins lymphoma (NHL) associated with an aggressive clinical course. Inhibition of the ubiquitin-proteasome pathway modulates survival and proliferation signals in MCL and has shown clinical benefit in this disease. This has provided rationale for exploring combination regimens with B-cell selective immunotherapies such as rituximab. In this study, we examined the effects of combined treatment with bortezomib and rituximab on patient-derived MCL cell lines (Jeko, Mino, SP53) and tumor samples from patients with MCL where we validate reversible proteasome inhibition concurrent with cell cycle arrest and additive induction of apoptosis. When MCL cells were exposed to single agent bortezomib or combination bortezomib/rituximab, caspase dependent and independent apoptosis was observed. Single agent bortezomib or rituximab treatment of Mino and Jeko cell lines and patient samples resulted in decreased levels of nuclear NFkappaB complex(es) capable of binding p65 consensus oligonucleotides, and this decrease was enhanced by the combination. Constitutive activation of the Akt pathway was also diminished with bortezomib alone or in combination with rituximab. On the basis of in vitro data demonstrating additive apoptosis and enhanced NFkappaB and phosphorylated Akt depletion in MCL with combination bortezomib plus rituximab, a phase II trial of bortezomib-rituximab in patients with relapsed/refractory MCL is underway.

Gastric duplication cysts in adults are very rare and usually found incidentally during evaluation for an unrelated ailment. When they are found in close proximity to the pancreas, they can be confused with cystic neoplasms of the pancreas, which are typically also asymptomatic yet more common. As part of the evaluation of cystic pancreatic lesions, cyst fluid analysis for carcinoem-bryonic antigen (CEA) is undertaken to determine malignant potential. Herein we present two cases of cystic lesions thought to arise from the pancreas found to have elevated preoperative cystic CEA levels. At operation, they were found to be gastric duplication cysts and were resected. We report the histologic findings and review of the current literature.

Background In vitro studies in mantle cell lymphoma (MCL) cell lines and patient-derived cells have demonstrated synergistic apoptosis with combined rituximab and bortezomib (R-bortezomib), compared to single agent bortezomib. Therefore, we evaluated R-bortezomib in a preclinical model and in a phase II clinical trial. Methods A Hu-MCL-SCID model engrafted with the Jeko cell line was treated with R-bortezomib, bortezomib, or rituximab. Twenty-five patients with relapsed follicular (n=11) and MCL (n=14) received 375 mg/m2 rituximab days 1 and 8 and 1.3-1.5 mg/m2 bortezomib days 1, 4, 8, and 11 every 21 days for a median of 3 cycles (range, 1-5). Results R-bortezomib resulted in a statistically significant improvement in overall survival in Hu-MCL-SCID mice. In the clinical trial, the overall response rate (ORR) in 25 patients was 40%, with an ORR of 55% and 29% in patients with follicular and MCL, respectively. The estimated 2-year progression-free survival (PFS) was 24% (95% CI 10%, 53%) in all patients and 60% (95% CI 20%, 85%) in responding patients. Thirteen patients (52%) developed grade 3 neurotoxicity consisting of constipation/ileus, sensory or motor neuropathy, or orthostatic hypotension. Patients heterozygous for the CD32a (Fcγ receptor IIa) 131 histidine (H) to arginine (R) polymorphism had a significantly decreased PFS (p=0.009) after R-bortezomib compared to HH and RR homozygotes. Conclusion R-bortezomib has significant activity in patients with relapsed or refractory follicular and MCL, although an unexpectedly high incidence of grade 3 neurologic toxicity is a potential limiting factor with this combination.