Fine‐needle aspiration of gray zone lesions of the breast: Fibroadenoma versus ductal carcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99655/1/dc22914.pd

SAG/ROC2 E3 ligase regulates skin carcinogenesis by stage-dependent targeting of c-Jun/AP1 and IκB-α/NF-κB

Sensitive to apoptosis gene (SAG)/regulator of cullins-2–Skp1-cullin–F-box protein (SCF) E3 ubiquitin ligase regulates cellular functions through ubiquitination and degradation of protein substrates. We report that, when expressed in mouse epidermis driven by the K14 promoter, SAG inhibited TPA-induced c-Jun levels and activator protein-1 (AP-1) activity in both in vitro primary culture, in vivo transgenic mice, and an AP-1– luciferase reporter mouse model. After AP-1 inactivation, epidermal proliferation induced by 7,12-dimethylbenz(a)-anthracene/12-O-tetradecanoylphorbol-13-acetate at the early stage of carcinogenesis was substantially inhibited. Later stage tumor formation was also substantially inhibited with prolonged latency and reduced frequency of tumor formation. Interestingly, SAG expression increased tumor size, not because of accelerated proliferation, but caused by reduced apoptosis resulting, at least in part, from nuclear factor κB (NF-κB) activation. Thus, SAG, in a manner depending on the availability of F-box proteins, demonstrated early-stage suppression of tumor formation by promoting c-Jun degradation, thereby inhibiting AP-1, and later-stage enhancement of tumor growth, by promoting inhibitor of κBα degradation to activate NF-κB and inhibit apoptosis

Statistics and clinical trials: The case of prednisolone in alcoholic hepatitis

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38385/1/1840160441_ftp.pd

Methods Used to Manage Urinary Incontinence by Older Adults in the Community

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111237/1/j.1532-5415.1989.tb05502.x.pd

P450 3A activity and cyclosporine dosing in kidney and heart transplant recipients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109917/1/cptclpt1994135.pd

Concurrent whole brain radiotherapy and bortezomib for brain metastasis

Abstract Background Survival of patients with brain metastasis particularly from historically more radio-resistant malignancies remains dismal. A phase I study of concurrent bortezomib and whole brain radiotherapy was conducted to determine the tolerance and safety of this approach in patients with previously untreated brain metastasis. Methods A phase I dose escalation study evaluated the safety of bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m2) given on days 1, 4, 8 and 11 of whole brain radiotherapy. Patients with confirmed brain metastasis were recruited for participation. The primary endpoint was the dose-limiting toxicity, defined as any ≥ grade 3 non-hematologic toxicity or grade ≥ 4 hematologic toxicity from the start of treatment to one month post irradiation. Time-to-Event Continual Reassessment Method (TITE-CRM) was used to determine dose escalation. A companion study of brain diffusion tensor imaging MRI was conducted on a subset of patients to assess changes in the brain that might predict delayed cognitive effects. Results Twenty-four patients were recruited and completed the planned therapy. Patients with melanoma accounted for 83% of all participants. The bortezomib dose was escalated as planned to the highest dose of 1.7 mg/m2/dose. No grade 4/5 toxicities related to treatment were observed. Two patients had grade 3 dose-limiting toxicities (hyponatremia and encephalopathy). A partial or minor response was observed in 38% of patients. Bortezomib showed greater demyelination in hippocampus-associated white matter structures on MRI one month after radiotherapy compared to patients not treated with bortezomib (increase in radial diffusivity +16.8% versus 4.8%; p = 0.0023). Conclusions Concurrent bortezomib and whole brain irradiation for brain metastasis is well tolerated at one month follow-up, but MRI changes that have been shown to predict delayed cognitive function can be detected within one month of treatment.http://deepblue.lib.umich.edu/bitstream/2027.42/112849/1/13014_2013_Article_928.pd

The prediction of radiationâ induced liver dysfunction using a local dose and regional venous perfusion model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134805/1/mp1081.pd

Predictors of toxicity in treating patients with neuroblastoma by radiolabeled metaiodobenzylguanidine

We searched for methods that would enable prescriptions of the maximum tolerable doses of iodine-131 metaiodobenzylguanidine (MIBG) and iodine-125 MIBG in the treatment of patients with neuroblastoma. We correlated doses, defined in different ways, with subsequent platelet levels in treated patients to determine accurate predictors of the most frequent toxicity, thrombocytopenia. Nine patients with neuroblastoma were given 131 I-MIBG (4.9–8.1 GBq or 132–220 mCi) and ten were given 125 I-MIBG (8.3-30.0 GBq or 224–809 mCi) as initial treatments. These therapies were sufficiently varied that correlations could be made between indices of the doses and the subsequent toxicity as reflected in circulating platelet levels. Predictors of toxicity were: whole-body absorbed dose of radiation (cGy) calculated from pretherapy tracer doses of 131 I-MIBG; GBq/kg of body weight; and GBq/m 2 of body surface area. Toxicity was recorded as the nadir of the platelet level and platelet/pretherapeutic level (platelet ratio). For treatments with 131 I-MIBG, the highest correlation was obtained between cGy and the logo 10 -transformed platelet ratio ( r =−0.86), but comparison of GBq/m2 and the platelet nadir ( r =−0.76) or the platelet ratio ( r =−0.74) or the log 10 − transformed platelet ratio ( r =−0.73) gave comparable and statistically significant results. For treatments with 125 I-MIBG, significant correlations were obtained between GBq/m 2 and the platelet ratio ( r =−0.81) or GBq/kg and the log 10 − -transformed platelet ratio; the correlation between cGy and any toxicity index was low. Per administered GBq, 131 I-MIBG was 2.6 times more potent than 125 I-MIBG in causing a platelet ratio of 0.1. Thus, in predicting toxicity, therapeutic doses of 131 I-MIBG expressed as GBq/m 2 performed satisfactorily and almost as well as whole-body cGy, and treatment doses of 125 I-MIBG expressed as GBq/m 2 or GBq/kg performed satisfactorily and much better than whole-body cGy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46835/1/259_2004_Article_BF00182305.pd

How Much Pharyngeal Exposure Is “Normal”? Normative Data for Laryngopharyngeal Reflux Events Using Hypopharyngeal Multichannel Intraluminal Impedance (HMII)

Laryngopharyngeal reflux (LPR) can cause atypical symptoms, asthma, and pulmonary fibrosis. The aim of this study was to establish the normative data for LPR using hypopharyngeal multichannel intraluminal impedancepH (HMII)