Protein Calorie Malnutrition, Nutritional Intervention and Personalized Cancer Care

Cancer patients often experience weight loss caused by protein calorie malnutrition (PCM) during the course of the disease or treatment. PCM is expressed as severe if the patient has two or more of the following characteristics: obvious significant muscle wasting, loss of subcutaneous fat; nutritional intake of \u3c50% of recommended intake for 2 weeks or more; bedridden or otherwise significantly reduced functional capacity; weight loss of \u3e2% in 1 week, 5% in 1 month, or 7.5% in 3 months. Cancer anorexiacachexia syndrome (CACS) is a multifactorial condition of advanced PCM associated with underlying illness (in this case cancer) and is characterized by loss of muscle with or without loss of fat mass. Cachexia is defined as weight loss of more than 5% of body weight in 12 months or less in the presence of chronic disease. Hence with a chronic illness on board even a small amount of weight loss can open the door to cachexia. These nutritional challenges can lead to severe morbidity and mortality in cancer patients. In the clinic, the application of personalized medicine and the ability to withstand the toxic effects of anti-cancer therapies can be optimized when the patient is in nutritional homeostasis and is free of anorexia and cachexia. Routine assessment of nutritional status and appropriate intervention are essential components of the effort to alleviate effects of malnutrition on quality of life and survival of patients

Dark Chocolate and Blood Pressure: A Novel Study from Jordan

Aim: The goal of this study was to assess the effect of dark chocolate intake on cardiovascular parameters like blood pressure and heart rate values in a normotensive population. Subjects and methods: This is a randomized crosssectional study involving a total of 14,310 adults that were selected from various regions of Jordan. Well-trained pharmacy students interviewed participants in the outpatient settings. Participants reported their weekly intake of dark chocolate that has been further classified into mild (1-2 bars/week), moderate (3-4 bars/week), and high intake ( \u3e 4 bars/week). For each participant, the systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate were measured three times with (10-15) minute intervals in the sitting position and the resting state. The arterial blood pressure (ABP) was calculated from the measured SBP and DBP values. Results: All measured blood pressure values were significantly decreased for participants who reported higher dark chocolate consumption. Our results showed that heart rate values were not affected by variable intake of dark chocolate. In addition, increasing dark chocolate intake was associated with a significant decrease of blood pressure values in participants irrespective of the family history of hypertension or the age of the individual. However, heart rate values were unaffected. Conclusion: Higher intake of dark chocolate can be associated with lower values of blood pressure, while its effect on heart rate values was not consistent

Dark Chocolate and Blood Pressure: A Novel Study from Jordan

Aim: The goal of this study was to assess the effect of dark chocolate intake on cardiovascular parameters like blood pressure and heart rate values in a normotensive population. Subjects and methods: This is a randomized crosssectional study involving a total of 14,310 adults that were selected from various regions of Jordan. Well-trained pharmacy students interviewed participants in the outpatient settings. Participants reported their weekly intake of dark chocolate that has been further classified into mild (1-2 bars/week), moderate (3-4 bars/week), and high intake ( \u3e 4 bars/week). For each participant, the systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate were measured three times with (10-15) minute intervals in the sitting position and the resting state. The arterial blood pressure (ABP) was calculated from the measured SBP and DBP values. Results: All measured blood pressure values were significantly decreased for participants who reported higher dark chocolate consumption. Our results showed that heart rate values were not affected by variable intake of dark chocolate. In addition, increasing dark chocolate intake was associated with a significant decrease of blood pressure values in participants irrespective of the family history of hypertension or the age of the individual. However, heart rate values were unaffected. Conclusion: Higher intake of dark chocolate can be associated with lower values of blood pressure, while its effect on heart rate values was not consistent

Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) comprises a group of aggressive and heterogeneous breast carcinoma. Chemotherapy is the mainstay for the treatment of triple-negative tumors. Nevertheless, the success of chemotherapeutic treatments is limited by their toxicity and development of acquired resistance leading to therapeutic failure and tumor relapse. Hence, there is an urgent need to explore novel targeted therapies for TNBC. Receptor tyrosine kinases (RTKs) are a family of transmembrane receptors that are key regulators of intracellular signaling pathways controlling cell proliferation, differentiation, survival, and motility. Aberrant activity and/or expression of several types of RTKs have been strongly connected to tumorigenesis. RTKs are frequently overexpressed and/or deregulated in triple-negative breast tumors and are further associated with tumor progression and reduced survival in patients. Therefore, targeting RTKs could be an appealing therapeutic strategy for the treatment of TNBC. This review summarizes the current evidence regarding the antitumor activity of RTK inhibitors in preclinical models of TNBC. The review also provides insights into the clinical trials evaluating the use of RTK inhibitors for the treatment of patients with TNBC

The Maxi-K (BK) Channel Antagonist Penitrem A as a Novel Breast Cancer-Targeted Therapeutic

Breast cancer (BC) is a heterogeneous disease with different molecular subtypes. The high conductance calcium-activated potassium channels (BK, Maxi-K channels) play an important role in the survival of some BC phenotypes, via membrane hyperpolarization and regulation of cell cycle. BK channels have been implicated in BC cell proliferation and invasion. Penitrems are indole diterpene alkaloids produced by various terrestrial and marine Penicillium species. Penitrem A (1) is a selective BK channel antagonist with reported antiproliferative and anti-invasive activities against multiple malignancies, including BC. This study reports the high expression of BK channel in different BC subtypes. In silico BK channel binding affinity correlates with the antiproliferative activities of selected penitrem analogs. 1 showed the best binding fitting at multiple BK channel crystal structures, targeting the calcium-sensing aspartic acid moieties at the calcium bowel and calcium binding sites. Further, 1 reduced the levels of BK channel expression and increased expression of TNF-α in different BC cell types. Penitrem A (1) induced G1 cell cycle arrest of BC cells, and induced upregulation of the arrest protein p27. Combination treatment of 1 with targeted anti-HER drugs resulted in synergistic antiproliferative activity, which was associated with reduced EGFR and HER2 receptor activation, as well as reduced active forms of AKT and STAT3. Collectively, the BK channel antagonists represented by penitrem A can be novel sensitizing, chemotherapeutics synergizing, and therapeutic agents for targeted BC therapy

Management of Sickle Cell Disease Pain among Adolescent and Pediatric Patients

Management of sickle cell pain in adolescent and pediatric patients is inadequate, and the employment of proper management guidelines and practices are highly variable among different regions and populations. APPT, the multidimensional adolescent pediatric pain tool, promotes optimal pain management and introduces best practical guidelines for pain management. The goal of this study is to assess pain and pain management among young patients diagnosed with sickle cell disease (SCD) by introducing the APPT as a tool for pain management, and analyze factors contributing to pain management. Information relevant to demographic data, SCD characteristics, APPT assessment, and satisfaction of patients regarding pain management were collected using a structured questionnaire. Results showed that SCD is highly associated with gender (p = 0.022), consanguinity (p = 0.012), and number of surgeries (p = 0.013). Most patients (58.9%) indicated the involvement of more than six body areas affected during pain crisis. Severe pain was described by more than half the patients (55.6%), while moderate pain was reported by 31.1%. Most patients described their pain by sensory, affective, and temporal words. The number of painful areas, pain intensity, and use of descriptive pain words was correlated and interpreted by age, BMI, school absence, and number of surgeries. Results of this study could provide guidance to healthcare providers to improve current practices for SCD pain management in order to improve health outcomes and patients’ satisfaction

HPLC with Fluorescence and Photodiode Array Detection for Quantifying Capmatinib in Biological Samples: Application to In Vivo and In Vitro Studies

Capmatinib, a recently approved tyrosine kinase inhibitor, is used for the treatment of non-small cell lung cancer. We describe two new HPLC methods for capmatinib quantification in vivo and in vitro. HPLC with a fluorescence detection method was used to quantify capmatinib in plasma for the first time. The method was successfully applied in a pharmacokinetic study following a 10 mg/kg oral dose of capmatinib given to rats. The chromatographic separation was performed using a Eurospher II 100-3 C18H (50 × 4 mm, 3 µm) column and a mobile phase containing 10 mM of ammonium acetate buffer (pH 5.5): acetonitrile (70:30, v/v), at a flow rate of 2.0 mL min−1. The study also describes the use of HPLC-PDA for the first time for the determination of capmatinib in human liver microsomes and describes its application to study its metabolic stability in vitro. Our results were in agreement with those reported using LC-MS/MS, demonstrating the reliability of the method. The study utilized a Gemini-NX C18 column and a mobile phase containing methanol: 20 mM ammonium formate buffer pH 3.5 (53:47, v/v), delivered at a flow rate of 1.1 mL min−1. These methods are suitable for supporting pharmacokinetic studies, particularly in bioanalytical labs lacking LC-MS/MS capabilities

Impact of Obesity on Clinicopathologic Characteristics and Disease Prognosis in Pre- and Postmenopausal Breast Cancer Patients: A Retrospective Institutional Study

Purpose. To investigate the association between obesity and breast cancer clinicopathologic characteristics at presentation along with prognostic impact among Jordanian breast cancer patients. Such data are lacking in Arabian countries. Methods. In this retrospective study, 348 breast cancer patients were included. Analyses were conducted for associations between body mass index (BMI) and age at diagnosis, tumor clinicopathologic characteristics, and molecular subtypes. Eight prognostic factors were considered, and total prognostic scores were calculated. The analysis was stratified by menopausal status. Multivariate logistic stepwise regression analysis was conducted to identify predictors for breast cancer recurrence and death. Results. Mean age at diagnosis was 50.98 ± 10.96 years. Mean BMI at diagnosis was 29.52 ± 5.32 kg/m2. Mean age at diagnosis was significantly higher for overweight and obese patients compared to underweight/normal patients (P<0.001). A significant positive correlation was observed between patient age and BMI at diagnosis (r = 0.251, P<0.001). Grade of carcinoma was significantly correlated with BMI in the whole population examined (P=0.003). Obese breast cancer patients had significantly higher prognostic scores compared to nonobese cases, indicating worse prognostic features at presentation (P=0.034). Stratification of data analysis based on menopausal status revealed significant associations between obesity and each of tumor stage and grade among postmenopausal but not premenopausal patients (P=0.019 and P=0.031, respectively). Similarly, postmenopausal obese patients had significantly higher prognostic scores compared to nonobese counterparts (P=0.007), indicating worse prognosis, a finding which was also absent among premenopausal breast cancer patients. No significant association between BMI with expression status of hormone receptors, HER2, lymphovascular invasion, and molecular subtypes was found among patients. BMI was a significant predictor for disease recurrence in which obese breast cancer patients had greater odds (2-fold) to develop locoregional and distant recurrence compared to nonobese cases (P=0.011). Conclusions. Obesity was associated with advanced stage and grade of breast carcinoma at diagnosis. The impact of BMI on clinicopathologic characteristics and prognosis was confined to postmenopausal cases. Jordanian obese breast cancer patients are at greater risk of breast cancer recurrence and reduced survival compared to their nonobese counterparts

(−)-Oleocanthal Prevents Breast Cancer Locoregional Recurrence After Primary Tumor Surgical Excision and Neoadjuvant Targeted Therapy in Orthotopic Nude Mouse Models

Breast cancer (BC) recurrence represents a challenge for survivors who have had their primary tumors surgically excised, and/or have completed radiation, neoadjuvant, or adjuvant therapeutic regimens. Current BC treatments mostly lack the ability to reduce the risk of disease recurrence. About 70% of BC patients will subsequently suffer disease relapse, manifesting as local, regional, or distant tumor recurrence, which clearly underscores the urgent need to discover novel recurrence inhibitors. (&#8722;)-Oleocanthal (OC) is a natural phenolic, found so far exclusively in extra-virgin olive oil (EVOO). OC exerts documented bioactivities against diverse cancer types, inflammation, and neurodegenerative diseases. Herein we report the novel activity of daily oral treatment with OC (10 mg/kg) in preventing BC locoregional recurrence in a nude mouse xenograft model generated by orthotopic inoculation with BT-474 cells as a luminal type B model. We further report inhibition of tumor recurrence by OC after completion of a lapatinib neoadjuvant regimen. However, in a recurrence model of triple-negative breast cancer (TNBC), OC treatment (10 mg/kg) did not effectively prevent tumor recurrence, but rather, was seen to significantly reduce the growth of recurrent tumors as compared to vehicle control-treated animals. Inhibition of tumor recurrence was associated with significant serum level reductions of the human BC recurrence marker CA 15-3 at the study end in animals treated with OC. OC treatment upregulated the expression of the epithelial marker E-cadherin and downregulated the levels of the mesenchymal marker vimentin in recurrent tumors vs. untreated control animals. OC treatment also reduced the activation of MET and HER2 receptors, as indicated by reduced phosphorylation levels of these proteins in recurrent tumors vs. controls. Collectively, the results of our studies provide the first evidence for suppression of BC tumor recurrence by oral OC treatment in an animal model for such recurrence, and furthermore, highlight favorable prospects for this natural product to emerge as a first-in-class BC recurrence inhibitor