Recent Advances in Understanding the Structure and Function Relationship of Multidrug Resistance-Linked ABC Transporter P-glycoprotein
Pages 88-98
Fei Zhou, Lothar Esser and Di Xia

DOI: http://dx.doi.org/10.6000/1929-2279.2016.05.03.2

Published: 23 August 2016

Abstract: Mammalian P-glycoproteins (P-gp) are members of the broad family of ABC transporters and play important physiological roles in establishing physical barriers that limit access of toxic compounds and thus in the pharmacokinetics of these compounds. Cancer cells exploit the presence of P-gp to fend off anti-cancer drugs, rendering them multidrug resistant (MDR). Structural investigations of P-gp involve the expression and isolation of this large integral membrane protein in high quality and in sufficient quantity for it to be amenable to electron microscopic (EM) and crystallographic studies. EM studies have defined the shape of the molecule and delineated its various conformations in solution but major breakthrough in obtaining atomic resolution structures of P-gp were accomplished by X-ray crystallography. Structures with increasing resolution and accuracy in various substrate and inhibitor bound forms are available for analysis and novel mechanistic insights have been obtained. These advances have paved the way for future research to further our understanding of the mechanism of P-gp function and development of potential inhibitors that may reverse MDR in cancer treatment.

Keywords: P-glycoprotein, ABC transporters, Multidrug Resistance, Mechanisms, Structures.

PET/CT and MRI in Evaluating Cervical Cancer
Pages 4-9
Runjun Shi, Jie Chen, Jinchang Wu and Jundong Zhou

DOI: http://dx.doi.org/10.6000/1929-2279.2016.05.01.1

Published: 29 January2016

Abstract: Positron emission tomography (PET)/computed tomography (CT) and magnetic resonance (MR) imaging are two most important imaging tools for evaluating cervical cancer in clinic. They have improved the accuracy of tumor staging and prognosis predicting in a large part. PET/CT is superior for lymph node (LN) status and metastasis to other imaging modalities. And it could differ among tumor types and grades according to maximum standardized uptake value (SUVmax). MRI is not sensitive to LN metastasis, but it shares the advantage of therapeutic response and recurrence evaluation with PET/CT. Recently, emerging functional imaging modality Diffusion-weighted imaging (DWI) has been showing its superiority on evaluation of cervical carcinoma as well. This article describes both advantages and limitations of MR imaging and PET/CT in evaluating cervical cancer, and reviews the current role of imaging techniques mentioned above.

Keywords: Positron emission tomography, magnetic resonance,cervical cancer, staging, treatment response, recurrence.

Concomitant Treatment for Brain Metastases in Non-Small Cell Lung Cancer Patients: Our Clinical Experience
Pages 23-28
S. Simonida Crvenkova and Maja Popova

DOI: http://dx.doi.org/10.6000/1929-2279.2016.05.01.5

Published: 29 January2016

Abstract: Purpose: Aim of this study was to evaluate tumor response, Quality of life (QoL) and median survival of concomitant chemotherapy (P/E) protocol with WBRT (whole brain radiotherapy) followed by P/E protocol until progression or appearance of serious adverse effects in NSCLC patients with multiple brain metastases.

Methods: From December 2012 to April 2014, 12 patients were enrolled in this study. All of the patients received previous treatments. Selected patients had multiple brain metastases detected on CT and/or MRI, and the brain is only one site of disease dissemination and patients were at younger age.

External beam radiotherapy was administered with two lateral opposed fields. Concurrently with WBRT, patients received P/E protocol and after 4 weeks, followed by P/E protocol repeated on 21 days until progression or appearance of serious adverse effects. Tumor response was assessed according to RECIST criteria. Assessment of QoL was performed by patients’ subjective answers, subjective improvement in emesis, ataxia, headache and seizures and without subjective improvement. Adverse effects were performed according to WHO criteria. Overall survival was analyzed from the beginning of the concomitant treatment until death or patient’s last control.

Results: Common adverse events were neurotoxicity and hematology toxicity according to WHO criteria. No patient was withdrawn from the study because of the adverse events. All patients reported subjective improvements. Overall median survival was 7.5 months (95% CI 6.32-8.73).

Conclusions: WBRT plus chemotherapy can improve the efficacy and QoL in NSCLC patients, because of synergistic effect and current evidence that the blood-brain barrier is damaged in patients with BM. Considering our clinical results, we recommend this treatment as safe and effective for selected NSCLC patients.

Keywords: Concomitant chemotherapy and WBRT, NSCLC patients, brain metastases.

A Guide for Pain Management in Developing Nations: The Diagnosis and Assessment of Pain in Cancer Patients
Pages 29-44
Joseph V. Pergolizzi, Gianpietro Zampogna, Robert Taylor, Marixa Guerrero, Juan Quillermo Santacruz and Robert B. Raffa

DOI: http://dx.doi.org/10.6000/1929-2279.2016.05.01.6

Published: 29 January2016

Abstract: The fundamental approach to cancer patients with pain is to identify the pain sites, and describe, quantify, and categorize the pain by type at each site. There are many validated tools to serve the clinician in these efforts, particularly for pain assessment. Multimechanistic pain syndromes are common in cancer patients. Cancer patients may experience nociceptive pain. They may also experience neuropathic pain due to chemotherapy-induced or cancer-related nerve damage. Analgesic choices must be guided by the pain mechanisms, nature, and severity of the pain, comorbid conditions, and patient characteristics. Long-acting opioid analgesics or fixed-clock dosing can eliminate end-of-dose analgesic gaps. The potential for opioid abuse is an important public health challenge but one that should not undermine the appropriate treatment of moderate to severe cancer pain. Abuse-deterrent opioid formulations can be useful. Care is needed for special populations of cancer patients dealing with pain, such as geriatric, pediatric, or obese patients. While morphine has long been the “gold standard” of oral opioid products, recent clinical trials suggest that oral hydrocodone and oral oxycodone may offer advantages over oral morphine. Patient adherence is crucial for adequate analgesia and patient education can promote adherence and manage expectations.

Keywords: Cancer pain, malignant pain, opioid analgesia, opioids, undertreatment of cancer pain, assessment of cancer pain.

¹⁸F-FDG PET/CT Imaging in Detection of Intravascular Large B-Cell Lymphoma
Pages 10-11
Fangyang Jiao, Jingjie Ge, Zhongwen Zhou, Yihui Guan and Chuantao Zuo

DOI: http://dx.doi.org/10.6000/1929-2279.2016.05.01.2

Published: 29 January2016

Abstract: Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma. Now, it remains a diagnostic challenge, because of non-specific findings on clinical, laboratory, and imaging studies. Here we present a case of an IVLBCL patient, who presented with fever of unknown origin and had skin involvement, that ¹⁸F-FDG PET/CT showed increased metabolism on systemic subcutaneous fat layer with a SUVmax of 1.29. After five courses of R-CHOP, 18F-FDG PET/CT showed disappearance of the diffuse FDG accumulation on systemic subcutaneous fat layer with a SUVmax of 0.55. These features make this case unique.

Keywords: Lymphoma, Fever, ¹⁸F-FDG, PET/CT.