Increasing the Efficacy of Doxorubicin Against Breast Cancer

In the United States, breast cancer accounts for one in three cancer diagnoses in women, making it the most common type of cancer in women. One important chemotherapeutic agent used to treat breast cancer is doxorubicin, an anthracycline compound that causes cell death by damaging DNA in addition to producing reactive oxygen species. Previously, the Berdis lab developed an artificial nucleoside analog designated 5-NIdR that improves the efficacy of DNA damaging agents used against brain cancer. This nucleoside works by inhibiting the replication of damaged DNA created by certain chemotherapeutic agents. In this project, we tested the ability of 5-NIdR to increase the efficacy of doxorubicin in the treatment of breast cancer. This was accomplished by comparing the effects of doxorubicin in the absence and presence of 5-NIdR using MCF-7 breast cancer cells and non-cancerous fibroblasts as models. Our studies show that breast cancer cells are highly resistant to doxorubicin, displaying an LD50 value of 840 nM which is 8-fold higher than that measured against non-cancerous fibroblasts (LD50 = 105 nM). Combining 5-NIdR with doxorubicin kills more cells compared to treatment with either doxorubicin or 5-NIdR used alone.https://engagedscholarship.csuohio.edu/u_poster_2018/1027/thumbnail.jp

Electrochemical Studies of Cobalt(II) diphenylazodioxide Complexes

The electrochemical behavior of the unusual cobalt(II) diphenylazodioxide complex salts [Co(az)4](PF6)2 1 and [Co(bpy)(az)2](PF6)2 2 has been studied by cyclic voltammetry. Each complex displays two quasireversible redox couples, which are proposed to correspond to a reduction of Co(II) to Co(I), followed by a ligand-based reduction. Irreversible reductions of 1 are observed at more negative potentials, and are proposed to arise from deposition of elemental Co and the decomposition of transiently formed Co(-I) species. Spectroelectrochemical experiments on both 1 and 2, involving electrolytic reduction followed by reoxidation, are consistent with the quasireversibility observed in the CV measurements

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Increasing the Efficacy of Doxorubicin Against Breast Cancer

In the United States, breast cancer accounts for one in three cancer diagnoses in women, making it the most common type of cancer in women. One important chemotherapeutic agent used to treat breast cancer is doxorubicin, an anthracycline compound that causes cell death by damaging DNA in addition to producing reactive oxygen species. Previously, the Berdis lab developed an artificial nucleoside analog designated 5-NIdR that improves the efficacy of DNA damaging agents used against brain cancer. This nucleoside works by inhibiting the replication of damaged DNA created by certain chemotherapeutic agents. In this project, we tested the ability of 5-NIdR to increase the efficacy of doxorubicin in the treatment of breast cancer. This was accomplished by comparing the effects of doxorubicin in the absence and presence of 5-NIdR using MCF-7 breast cancer cells and non-cancerous fibroblasts as models. Our studies show that breast cancer cells are highly resistant to doxorubicin, displaying an LD50 value of 840 nM which is 8-fold higher than that measured against non-cancerous fibroblasts (LD50 = 105 nM). Combining 5-NIdR with doxorubicin kills more cells compared to treatment with either doxorubicin or 5-NIdR used alone.https://engagedscholarship.csuohio.edu/u_poster_2018/1027/thumbnail.jp

Acute keratoconjunctivitis associated with tisotumab vedotin-tftv for metastatic cervical cancer

Purpose: Tisotumab vedotin-tftv, an antibody-drug conjugate, was recently FDA-approved for metastatic or treatment-resistant cervical cancer. A high rate of ocular comorbidities was seen in pivotal clinical trials. We present a case of a 46-year-old woman who experienced prolonged ocular surface adverse effects associated with use of the drug. Observations: Our patient was initiated on tri-weekly 2mg/kg infusions of tisotumab for metastatic cervical cancer. Baseline ophthalmic exam was unremarkable. One week after the second infusion, she developed bilateral eyelid edema and chalazia managed with initiation of lid hygiene measures. Preceding the fourth infusion, she developed unilateral pseudomembranous conjunctivitis and bilateral meibomitis that improved with topical corticosteroids. The fifth infusion was subsequently given at a reduced dosage. Despite this, she experienced decreased vision, bilateral diffuse punctate epitheliopathy, and subepithelial haze. The patient was subsequently referred to the cornea service. Symptomatic and clinical improvement was initially achieved with the addition of bandage contact lenses (BCLs). As the keratitis improved, topical steroids were tapered and BCLs removed. She is currently maintained on a regimen that includes eyelid hygiene, preservative-free artificial tears, punctal plugs, autologous serum tears, and lifitegrast. Given the severity of the ophthalmic adverse effects, however, further tisotumab infusions were held. Conclusions and importance: This is a report of a patient with prolonged ocular surface disease following the initiation of tisotumab, significant enough to lead to discontinuation. Antibody-drug conjugates are an emerging class of therapeutics across oncology, and ophthalmologists should be aware of their potential effects on ocular health

Electrochemical Studies of Cobalt(II) diphenylazodioxide Complexes

The electrochemical behavior of the unusual cobalt(II) diphenylazodioxide complex salts [Co(az)4](PF6)2 1 and [Co(bpy)(az)2](PF6)2 2 has been studied by cyclic voltammetry. Each complex displays two quasireversible redox couples, which are proposed to correspond to a reduction of Co(II) to Co(I), followed by a ligand-based reduction. Irreversible reductions of 1 are observed at more negative potentials, and are proposed to arise from deposition of elemental Co and the decomposition of transiently formed Co(-I) species. Spectroelectrochemical experiments on both 1 and 2, involving electrolytic reduction followed by reoxidation, are consistent with the quasireversibility observed in the CV measurements