Recurrent Oral Cancer: Current and Emerging Therapeutic Approaches.

Recurrent oral cancer: current and emerging therapeutic approaches.

Filed under: Drug and Alcohol Rehabilitation

Front Pharmacol. 2012; 3: 149
da Silva SD, Hier M, Mlynarek A, Kowalski LP, Alaoui-Jamali MA

Oral cavity cancer (OCC) is associated with high incidence of loco-regional recurrences, which account for the majority of treatment failures post-surgery and radiotherapy. The time-course of relapse manifestation and metastasis are unpredictable. Relapsed OCC represents a major clinical challenge in part due to their aggressive and invasive behaviors. Chemotherapy remains the only option for advanced OCC whenever salvage surgery or re-irradiation is not feasible, but its efficacy is limited as a result of the drug resistance development. Alternatives to use of different permutations of standard cytotoxic drugs or combinations with modulators of drug resistance have led to incremental therapeutic benefits. The introduction of targeted agents and biologics against selective targets that drive cancer progression has opened-up optimism to achieve superior therapeutic activity and overcome drug resistance because, unlike the non-selective cytotoxic, the target can be monitored at molecular levels to identify patients who can benefit from the drug. This review discusses the multifactorial aspects of clinical drug resistance and emerging therapeutic approaches in recurrent OCC, emphasizing recent advances in targeted therapies, immunotherapy, and potential relevance of new concepts such as epithelial-mesenchymal transition and cancer stem cell hypothesis to drug resistance.
HubMed – drug

 

A Case of Paclitaxel-induced Maculopathy Treated with Methazolamide.

Filed under: Drug and Alcohol Rehabilitation

Korean J Ophthalmol. 2012 Oct; 26(5): 394-7
Koo NK, Kim YC

A 54-year-old female patient who had been undergoing anti-cancer chemotherapy and radiotherapy for seven years after surgery for left breast cancer visited our clinic for visual disturbance in the right eye at nine months after paclitaxel administration. The best-corrected visual acuity was 0.5 in the right eye and 1.0 in the left eye. The patient was diagnosed with maculopathy due to paclitaxel administration based on the finding of cystoid macular edema in the right eye on fundus examination and optical coherence tomography; however, no leakage was detected on fluorescein angiography. Thus, drug replacement was planned. On the other hand, no abnormal finding was observed in the left eye. However, as the anti-cancer effect of paclitaxel is significant, replacing paclitaxel with another agent was not warranted; therefore, maintenance therapy with methazolamide was performed before and after administering the anti-cancer agent. Aggravation of cystoid macular edema was prevented, and vision improvement was achieved by oral maintenance therapy with methazolamide. In addition, the same fundus findings as shown in the right eye were detected in the left eye at 16 months after paclitaxel administration. After administering methazolamide, macular thickness was reduced, and vision was improved in the left eye. Paclitaxel administration was discontinued due to cutaneous metastasis from the breast cancer, and another anti-cancer agent was then administered. No subsequent cystoid macular edema has occurred.
HubMed – drug

 

Selaginella tamariscina water extract inhibits receptor activator for the nuclear factor-?B ligand-induced osteoclast differentiation by blocking mitogen-activated protein kinase and NF-?B signaling.

Filed under: Drug and Alcohol Rehabilitation

Pharmacogn Mag. 2012 Jul; 8(31): 184-91
Shim KS, Kang JS, Lee MH, Ma JY

Selaginella tamariscina has been traditionally used in Korea for treating hematochezia, hematuria, and prolapse of the anus. The aim of this study was to evaluate the inhibitory effect of Selaginella tamariscina water extract (ST-WE) on osteoclast differentiation, and to determine the underlying molecular mechanism.RAW264.7 cells were used as a model to examine receptor activator for the nuclear factor-?B ligand (RANKL)-induced osteoclast differentiation. Expression of osteoclastic genes and transcription factors was evaluated by real-time quantitative polymerase chain reaction (QPCR). Activation of the mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, and NF-?B were determined by Western blot analysis.ST-WE significantly inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity and formation of multinucleated osteoclasts in RAW264.7 cells. ST-WE also significantly inhibited the RANKL-induced mRNA expression of TRAP, cathepsin K, and the d2 isoform of vacuolar ATPase V(0) domain (ATPv0d2) gene. In addition, ST-WE inhibited the RANKL-induced phosphorylation of ERK, JNK, and p38, phosphorylation of I-?B(?) and NF-?B p65, and the expression of transcription factors c-fos, Fra-2, and nuclear factor of activated T cells 1. Furthermore, ST inhibited the bone resorptive activity of osteoclasts.ST-WE might have beneficial effects on bonedisease by inhibiting osteoclastogenesis and osteoclastic activity.
HubMed – drug

 

Drug resistance beyond XDR-TB: results from a large individual patient data meta-analysis.

Filed under: Drug and Alcohol Rehabilitation

Eur Respir J. 2012 Oct 11;
Migliori GB, Sotgiu G, Gandhi NR, Falzon D, Deriemer K, Centis R, Hollm-Delgado MG, Palmero D, Pérez-Guzmán C, Vargas MH, D’Ambrosio L, Spanevello A, Bauer M, Chan ED, Schaaf HS, Keshavjee S, Holtz TH, Menzies D,

The broadest pattern of tuberculosis drug resistance for which a consensus definition exists is extensively drug-resistant tuberculosis (XDR-TB). It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance to explore the need for a new definition.Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR-alone and three non-mutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) capreomycin and kanamycin/amikacin (XDR+2sli); XDR plus resistance to second-line injectables and to ?1 Group 4 drug, i.e.: ethionamide/prothionamide, cycloserine/terizidone or PAS (XDR+sliG4); and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ).Of 405 XDR-TB cases, 301 were XDR-alone; 68 XDR+2sli; 48 XDR+sliG4; and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted Odds Ratio (aOR): 0.4; 95% Confidence Interval: 0.2-0.8) compared to XDR-alone, while odds of failure+death were higher in all XDR patients with additional resistance (aOR range: 2.6-2.8).Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current DST methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.
HubMed – drug

 

Behavior and anti-glioma effect of lapatinib-incorporated lipoprotein-like nanoparticles.

Filed under: Drug and Alcohol Rehabilitation

Nanotechnology. 2012 Oct 11; 23(43): 435101
Gao H, Yang Z, Cao S, Xi Z, Zhang S, Pang Z, Jiang X

The purpose of the investigation was to prepare a new type of nanoparticle, namely lapatinib-incorporated lipoprotein-like nanoparticles (LTNPs), and to evaluate the behavior and anti-glioma effect of LTNPs. LTNPs were prepared and characterized using the Cyro-transmission electron microscope (Cryo-TEM) and Raman scan methods. Cellular uptake and subcellular localization studies were performed to evaluate the in vitro behavior of LTNPs. An in vivo imaging technique was used for the evaluation of the targeting of LTNPs. To study the anti-glioma effect, glioma xenografts were used. The particle size of LTNPs was 92.6 nm, and the zeta potential was 28.40 mV. LTNPs contained a surface layer that was obviously different from the core, according to the Cryo-TEM analysis. A Raman scan analysis demonstrated the incorporation of lapatinib in LTNPs, and it also revealed a structure different from free lapatinib. The uptake of LTNP by U87 cells occurred in a concentration- and time-dependent manner. According to the subcellular study, the uptake of LTNPs was endosome mediated. LTNPs could distribute and accumulate in the tumor site by an enhanced permeation and retention effect. Both LTNPs (10 mg kg(-1)) and LTNPs (30 mg kg(-1)) could significantly inhibit the growth of U87 xenografts. For a similar antitumor effect, the required cumulative dose of LTNPs was only 5% compared to that of Tykerb (the commercial formulation of lapatinib). This study demonstrated the effective uptake of LTNPs by U87 cells, the passive targeting of LTNPs at tumors and the better antitumor effect of LTNPs.
HubMed – drug

 


 

PART1 Alcoholism and Diet Talk at Hawthorn University www.ChefOfThePeople.com – Join Chef Of The People Nathan Donahoe (www.ChefOfThePeople.com) as he gives a talk at Hawthorn University (www.hawthornuniversity.org) on his experience of working as Executive Chef and nutritionist at drug and alcohol rehabilitation centers in Malibu California. Learn such juicy tidbits as what organic, natural foods help heal alcoholism and addiction and what foods hurt.

 

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