The Use of Herbal Therapy to Improve the Quality of Life among Cancer Patients in the Southern Region of Peninsular Malaysia

Objective: To investigate the impact of herbal therapy on the quality of life (QoL) among cancer patients and to evaluate the relationship of QoL with age, gender, cancer stage, cancer type, and history of conventional treatment.Methodology: A prospective study was targeted on cancer patients receiving herbal therapy from a Traditional and Complementary Medicine (T&CM) clinic in a public hospital from 1st January 2016 to 31st August 2018. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTCQLQ-C30) was distributed to the patients prior to herbal therapy (baseline) and after the sixth and twelfth week of herbal therapy. Socio-demographic and clinical data were collected and analyzed using SPSS version 16. Results: The majority of the patients were females (60.0%) and were from the Chinese ethnic group (77.4%) with a mean age of 58.72 ± 12.17 years. Approximately 42.4% of patients were in advanced cancer stages at the time of study and 60.7% of patients had undergone radiotherapy before receiving herbal therapy. The most commonly prescribed herbs were Bai Hua She She Cao (90.6%) and Zhen Ren Huo Ming Yin (57.6%). Significant differences in mean score were observed in global health status, overall functional scales, and symptom scales after the sixth and twelfth week of receiving herbal therapy. QoL in terms of global health status and overall functional scales improved with higher scores while symptom scales recorded a lower score after twelve weeks of receiving herbal therapy in the T&CM clinic. Herbal therapy has a significant effect (p < 0.05) on the improvement of QoL of cancer patients. However, gender, cancer stage, cancer type, age, history of radiotherapy, and history of chemotherapy has no effect (p > 0.05). Conclusion: Herbal therapy did improve the QoL of cancer patients in the southern region of Peninsular Malaysia.     

Breast Cancer Risk From Modifiable and Non-Modifiable Risk Factors among Palestinian Women: A Systematic Review and Meta-Analysis

Objective: Breast cancer (BC) is known as one of the deadliest forms of cancer, and it is increasing globally. Identifying risk factors for BC is a key point in developing preventive strategies to reduce its occurrence. Herein, we aimed to conduct a systematic review and meta-analysis focus on the risk factors for BC in Palestine. Material and Methods: We performed a systematic search via PubMed, MEDLINE, SCOPUS, Science Direct, Cochrane library, Emerald Insight, and Google scholar for identifying studies published on BC risk factors up to March 2021. Pooled odds ratios (OR) are calculated using fixed and random-effect models. Data were processed using Review Manager 5.4 (RevMan 5.4). Results: From a total of 73 articles, seven case-control studies met the criteria for systematic review. Meta-analysis results showed that of the known modifiable risk factors for BC, diabetes mellitus (DM) had the highest odds ratio (OR = 4.97, 95% CI 3.00- 8.25) followed by hypertension (OR = 3.21, 95% CI 1.96-5.23), obesity (BMI >30 Kg/m2) (OR = 2.90, 95% CI 2.00- 4.21), and passive smoking (OR = 1.50, 95% CI 1.12- 2.02). Controversially, breastfeeding (OR = 0.37, 95% CI 0.23- 0.61) was protective factor in BC. Of non-modifiable risk factors for BC has reached menopause had the highest odds ratio (OR = 3.74, 95% CI 2.64- 5.29), followed by family history of BC (OR = 2.63, 95% CI 1.07-6.44) and age (≥ 40 years) (OR = 2.49, 95% CI 1.43-4.34). Conclusions: The most significant predictors of BC in Palestine were DM, hypertension, passive smokers, age (>40), reached menopause, and family history of BC. Almost all these risk factors are consistent with known risk factors for breast cancer in other parts of the world.     

MiRNA-Mediated Knock-Down of Bcl-2 and Mcl-1 Increases Fludarabine-Sensitivity in CLL-CII Cells

Background: Over-expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1 is associated with resistance to chemotherapeutic agents such as fludarabine. Moreover, an inverse relationship between miRNA-15a levels with Bcl-2 and Mcl-1 expression has been observed in CLL patients. In this study, the effect of miRNA-15a on apoptosis and sensitivity of the CLL cells to fludarabine was investigated. Methods: After treatments, the Mcl-1 and Bcl-2 expression levels were quantified by RT-qPCR. Trypan blue assay was used to explore the effects of miRNA-15a and fludarabine on cell proliferation. The cytotoxicity was measured using MTT assay and combination index analysis. Cell death was determined using cell death detection ELISA assay and caspase-3 activity assay Kits. Results: Results showed that miRNA-15a clearly decreased the mRNA levels of Bcl-2 and Mcl-1 in a time dependent manner, which led to CLL-II cell proliferation inhibition and enhancement of apoptosis (p < 0.05, relative to control). Transfection of the miRNA-15a synergistically reduced the cell survival rate and lowered the IC50 value of fludarabine. Furthermore, miRNA-15a significantly enhanced the apoptotic effect of fludarabine. Conclusions: Our data propose that suppression of Bcl-2 and Mcl-1 by miRNA-15a can effectively inhibit the cell proliferation and sensitize CLL cells to fludarabine. Therefore, miRNA-15a can be considered as a potential therapeutic target in CLL resistant patients.     

Anti-Proliferative Effect of Doxorubicin-Loaded AS1411 Aptamer on Colorectal Cancer Cell

Background: Doxorubicin (Dox) inhibits DNA replication and causes DNA damage resulting in cell death. It is a common drug for treatment of many cancers. Treatment efficacy and side effects of Dox are critical issues in using it because the drug lacks of specificity. The objective of this study was to improve the specificity of Dox by the incorporation of this drug with AS1411 aptamer (ASA). Methods: Dox was intercalated into the duplex sites of ASA, a recognition molecule for a number of cancer cells, and formed Dox-loaded ASA. The recognition ability proceeded through specific binding between the aptamer and nucleolin overexpressed in the cancer cells. The tested cells were human colorectal adenocarcinoma cell line (SW480) and human normal colon cell CCD841 CoN (CCD841). Binding of ASA to the cells was tested using flow cytometer and fluorescence microscope. Intercalation of Dox into DNA duplex was confirmed by fluorescence spectrometry. Effect of ASA, Dox, and Dox-loaded ASA on cell viability was examined by cell proliferation assay. Caspase-3 activation was analyzed by western blotting. Results: ASA bound specifically to SW480 cells via interaction between the aptamer and nucleolin because the nucleolin was highly expressed in SW480 cells. ASA decreased the viability of SW480 cells in a dose-dependent manner. Dox was more toxic than ASA. Fluorescence quenching revealed that Dox was able to intercalate in base pairing sites of the aptamer. Dox-loaded ASA inhibited the proliferation of SW480 cells, because the aptamer facilitated the Dox uptake into these cells which caused the cell apoptosis, indicated by the significant decrease in procaspase-3, apoptosis marker protein. Conclusion: This study succeeded to prepare Dox-loaded ASA by intercalation of the drug that inherited the binding function from the aptamer and anti-cancer activity from Dox. Dox-loaded ASA showed promise for effective cancer treatment with lower level of side effects.     

A Meta-Analysis for Association of XRCC1, XRCC2 and XRCC3 Polymorphisms with Susceptibility to Thyroid Cancer

Background: We conducted a comprehensive meta-analysis to explore the association of polymorphisms at XRCC1, XRCC2 and XRCC3 genes with susceptibility to thyroid cancer (TC). Methods: We searched PubMed, EMBASE, Web of Science, and CNKI for relevant available studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the associations. Results: A total of 67 studies including 17 studies with 6,806 cases and 5,229 controls on XRCC1 Arg399Gln, 13 studies with 3,234 cases and 4,807 controls on XRCC1 Arg280His, 13 studies with 2,956 cases and 3,860 controls on XRCC1 Arg194Trp, five studies with 1,287 cases and 1,422 controls on XRCC2 Arg188His, 13 studies with 2,488 cases and 3,586 controls on XRCC3 Thr241Met, and six studies with 1,828 cases and 2,060 controls on XRCC3 IVS5-14 polymorphism were selected. Polled data revealed that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His and XRCC3 Thr241Met and IVS5-14 polymorphisms were not significantly associated with an increased risk of TC. Stratified analyses by ethnicity showed that the XRCC1 Arg399Gln polymorphism was associated with TC risk in Caucasians, but not in Asians. Conclusions: Our meta-analysis indicated that the XRCC1 Arg399Gln, Arg280His, Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met and IVS5-14 polymorphisms were not associated with risk of TC in the global population.  Further well-designed investigations with large sample sizes are required to confirm our results.     

Evaluation of Role of Visual Inspection Using Acetic Acid (VIA) and Exfoliative Cytology in Screening and Early Detection of Oral Premalignant Lesions and Oral Cancer

Objective: Oral cancer accounts for 50–70% of total cancer mortality. VIA screening has drastically changed the morbidity and mortality related to cervical cancer. In present study, we assessed the role of 5% Acetic Acid as a vital stain in oral mucosa of chronic tobacco chewers, to know if it can help in early diagnosis and improved prognosis of oral malignancies and to assess the sensitivity and specificity of VIA and exfoliative cytology for screening of Oral premalignant and malignant lesions in high risk population with limited health care infrastructure. Methods: This was an outpatient department based prospective study done in a tertiary hospital over a period of two years. 150 cases with a history of chronic tobacco use were evaluated. Visual inspection (VI) followed by VIA using 5% Acetic acid was done. Oral scrapes were taken for cytological examination followed by biopsy for histopathological evaluation, wherever possible. Results: Sensitivity, specificity, PPV, NPV and accuracy of VIA and Exfoliative cytology was 71%, 65%, 83%, 48%, 69% and 98%, 65%, 89%, 92%, 88% respectively keeping histology as gold standard. Conclusion: Acetic acid along with exfoliative cytology can be used as simple, cost effective and convenient methods for mass screening of OPMDs and OSCC in high risk population where biopsy is not possible.     

Uncovering Philip Morris International’s Fundamental Strategies for Product Placement in Thailand: Spotlighting Industry Penetration to Advance the Endgame

Background: Tobacco companies and their associated businesses know that placement – where one can see and purchase their products – is critical to their success. Placement is one of the four fundamental Ps of marketing along with product, price and promotion. Placement includes identifying retail locations in important places such as in shopping districts, within neighborhoods, near schools, at beaches, and in parks. In Southeast Asia, counteracting tobacco company placement strategies that result in market penetration is essential to advancing the endgame, namely ending tobacco use. However, in Southeast Asia research on the placement of tobacco products has been limited. Objectives: We undertook to analyze how Philip Morris International (PMI) through its subsidiary Philip Morris Asia Inc. (PMAI), from the time the company entered Thailand’s market once it was forced open in 1990, developed its successful product placement strategies and tactics. Methods: We examined over 4,000 PMI and PMAI internal documents using an historical, iterative and thematic approach. We analyzed the most relevant and illuminating documents, particularly those in which PMAI discussed retailer supply, retailer acceptance and retailer cooperation. Results: Even before foreign tobacco brands were legally allowed to be sold in Thailand, PMAI was already doing customer research in Thailand. In 1989, PMAI conducted a study of potential Thai customers in which 24% of respondents’ lack of availability (i.e., product placement) was one of the main reasons for not smoking PMI’s products. Based on these findings, PMAI engaged in intensive internal efforts to address the placement barrier to gain share. PMAI placed considerable emphasis on “stimulating retail trade acceptance” by making payments to retailers who met agreed upon and contracted product sales targets. PMAI’s initial successes incentivizing Thai retailers by essentially buying prime retail space for placement of their brands, to crowd out local and other foreign brands, became the foundation of what evolved into a sophisticated program to make placement highly lucrative for retailers. Conclusion: PMAI viewed aggressive product placement as essential to success as a new entrant in Thailand, and their product placement strategies contributed substantially to capturing a large share of the market. Therefore, endgame strategies must focus on restricting product placement through surveillance of tobacco industry legal, investment and retailer actions and through stricter tobacco retailer licensing requirements and penalties.     

Feasibility and Efficacy of Inspiratory Muscle Training in Patients with Head and Neck Cancer receiving Concurrent Chemoradiotherapy

Objectives: Patients with head and neck cancer (HNC) undergoing concurrent chemoradiotherapy (CCRT) often experience pulmonary symptoms. This study evaluated if a 7-week inspiratory muscle training (IMT) program during CCRT is feasible, adherent, and safe in patients with HNC. This study also evaluated the effect of IMT on diaphragm thickness, mobility, and cardiorespiratory parameters in patients with HNC receiving CCRT. Methods: Ten participants with advanced stage HNC receiving CCRT were recruited for the study. Feasibility, adherence, and safety of the intervention were the primary outcomes. Changes in diaphragm thickness and mobility, maximal inspiratory pressure, maximal expiratory pressure, forced vital capacity, forced expiratory volume in first second and functional capacity using 6-MWT were measured at baseline and post 7 weeks of CCRT. IMT was performed at one session per day for 5 days a week for 7 weeks. Eight sets of two minutes of inspiratory manoeuvres with one minute rest period between them with intensity of 40% MIP were given. Results: Ten participants  were included in this study out of the 13 patients screened, indicating the feasibility to be 76.9%. Participants completed a total of 260 training sessions out of the 350 planned sessions denoting the adherence level as 74%. Diaphragm thickness and MEP remained significantly unchanged while significant decline was seen in diaphragm mobility, MIP,FVC, FEV1 and 6-MWD at the end of 7 weeks. No adverse events were reported following the intervention. Conclusion: Inspiratory muscle training did not show significant effect on the diaphragm thickness, mobility, and cardiorespiratory parameters; however, it was feasible, adherent, and safe in patients with HNC receiving CCRT.     

Role of Resveratrol as Radiosensitizer by Targeting Cancer Stem Cells in Radioresistant Prostate Cancer Cells (PC-3)

Aim of Work: Here, we examined the role of resveratrol as a radiosensitizer by targeting cancer stem cells in radioresistant prostate cancer cells (PC-3) using stem cell markers CD44, CD49b and CD29, SOX2, OCT4, CXCR4, DCLK1 and EMT markers such as VIM and E-cadherin. Material and Methods: This study was an in vitro study involving PC-3 cell line which was dividing into four groups. Group I (CO): Control group composed of cells grown in the same medium without treatment with ionizing radiation or resveratrol. Group II (IR): Cells were treated with ionizing radiation alone. Group III (RV): Cells were treated with resveratrol alone. Group VI (IR&RV): The cells were treated with ionizing radiation and resveratrol in combination. The viability of cells was assessed by MTT assay. Genes of interest were measured by RT-PCR and the radiosensitizing efficacy of RV on proliferating cancer cells was determined by clonogenic assay. Results: Ionizing radiation significantly reduced PC-3 viability, lowered stem cell markers and affected epithelial to mesenchymal transition (EMT) genes expression at all doses (2, 4, 6 and 8 Gray). Resveratrol significantly decreased PC-3 viability and lowered stem cell markers and EMT genes expression at concentrations 35, 70 and 140 µM. Combining resveratrol treatment with ionizing radiation leads to significant reduction in cell viability and stem cell markers genes which was noticed with increasing the radiation dose when compared to ionizing radiation alone treated group. Conclusion: Resveratrol has a radiosensitizing effect, that ability is triggered by reducing the expression of cancer stem cell markers and affecting EMT markers. Resveratrol showed to be a good candidate for further studies as anticancer drug in the treatment of human prostate cancer.     

The Effect of Gene Mutations on Metastasis and Overall Survival in Metastatic and Nonmetastatic Colon Cancers

Objective: It is known that many genes are associated with colon cancer. We aimed to investigate the effect of gene mutations on metastasis and overall survival in metastatic and non metastatic colon cancers. Methods: A total of 50 patients with metastatic (n=25) and non metastatic (n=25) diagnosed with colon cancer between 2010 and 2018 were included in the study. APC, MUTYH, RAD50, MEN1, ATM, PALB2, NSH2, BRCA1, BRCA2, MLH1, BRIP1, TP53, PTEN, BARD1, MSH6, PMS2, NBN, and FAM175A gene mutations were evaluated using the next generation sequencing method. The effect of gene mutations on metastasis and overall survival were evaluated. Results: The mean age of patients with colon cancer without distant metastasis was 48.64±14.72 years and for patients with distance metases was 56.68±11.65. The mean survival time of colon cancer patients with distant organ metastasis after the metastasis date was 104.36±58.59 weeks. The presence of APC, MUTYH, and TP53 genetic mutations was observed with a higher rate in metastatic colon cancer (p<0.05). Conclusion: We showed that APC, MUTYH, and TP53 mutations are associated with distant organ metastasis.