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Changes in cellular immunity during chemotherapy for primary breast cancer with anthracycline regimens

Wijayahadi N, Haron MR, Stanslas J, Yusuf Z

J Chemother, 2007 Dec;19(6):716-23.
PMID: 18230556

Anthracyclines are the most widely used anticancer agents for breast cancer, of which doxorubicin and epirubicin have been reported to have equal efficacy. Unfortunately, the integrity of the immune system of breast cancer patients is severely affected by chemotherapy. This study compared the effect of combination chemotherapy with epirubicin (5-fluorouracil, epirubicin, cyclophosphamide (FEC)) and doxorubicin (5-fluorouracil, doxorubicin, cyclophosphamide (FDC)) regimens on subsets of the immune cells of patients with primary malignant breast tumors. Our aim was to determine the best regimen that produces the least degree of myelosuppression. Blood from 80 breast cancer patients undergoing chemotherapy (40 FEC and 40 FDC) was taken before chemotherapy and after every cycle (3 weeks) for 6 cycles. Blood was also taken from 40 normal healthy donors who served as normal control. Subsets of lymphocytes T-helper cells (CD3(+)CD4(+)), T-cytotoxic cells (CD3(+) CD8(+)), B-cells (CD19(+) CD20(+)) and NK cells (CD16(+)/CD56(+)CD3(-)) were analyzed by flow cytometry (FacsCalibur, BD) using monoclonal antibodies (Multitest, BD). All patients in the FEC and FDC groups suffered from myelosuppressive side effects. Both regimens led to an increase in the counts of monocytes but decreased polymorphonuclear cells (PMNs) and lymphocytes. Percentages of T-cytotoxic cells and NK cells were increased, but the percentage of B-cells was dramatically decreased. The phagocytic and intracellular killing ability of PMNs were also suppressed (p<0.01). No significant difference was found between the epirubicin-based regimen and doxorubicin-based regimen with regard to numbers of immune cells, percentages of lymphocytes subsets, Th/CTL ratio, engulfment and killing abilities of PMNs. In conclusion, we found that the epirubicin-based regimen is not superior to the doxorubicin-based regimen with respect to their toxicity of the immune cells, Th/CTL ratio and PMN count and functions. Moreover, both FEC and FDC regimens appear to conserve the cell-mediated immunity response needed for fighting against cancer cells.
Fulltext Ondansetron against metoclopramide/dexamethasone--a comparative study

Lim AKH, Haron MR, Yap TM

Med J Malaysia, 1994 Sep;49(3):231-8.
PMID: 7845271

This trial was carried out in Hospital Kuala Lumpur. Fifty-two patients who were scheduled to receive their first or subsequent courses of cancer chemotherapy with single dose cisplatinum containing chemotherapy regimens were evaluated. Thirty-four patients were given ondansetron in one group while 18 in the other group received metoclopramide with dexamethasone. The response to treatment was categorised as complete (0 emetic episode), major (1 or 2 emetic episodes), minor (3 to 5 emetic episodes) or failure (> 5 emetic episodes or rescue medication). Among the 52 patients, a complete or major control (0 to 2 emetic episodes) was achieved in 23/34 patients (68%) from the ondansetron group and in 3/18 patients (17%) from the metoclopramide with dexamethasone group (p < 0.002) on day 1. Similarly, the control of nausea was greater in the ondansetron group compared with the metoclopramide with dexamethasone group (p < 0.0009) on day 1. Two patients were excluded (dropped out) after day one from each of the two study groups due to excessive vomiting subsequent to cisplatinum therapy. From days 2 to 6, there was a trend in favour of ondansetron. Both treatments were well tolerated. The results of this trial show that in the prophylaxis of nausea and vomiting induced by cisplatinum containing chemotherapy, the efficacy of ondansetron is superior to that of a standard anti-emetic combination, metoclopramide with dexamethasone.
Randomized Controlled Trial on the Effect of Partially Hydrolyzed Guar Gum Supplementation on Diarrhea Frequency and Gut Microbiome Count Among Pelvic Radiation Patients

Rosli D, Shahar S, Manaf ZA, Lau HJ, Yusof NYM, Haron MR, et al.

JPEN J Parenter Enteral Nutr, 2021 02;45(2):277-286.
PMID: 32740950 DOI: 10.1002/jpen.1987

BACKGROUND: Radiation therapy is the treatment of pelvic cancers, with diarrhea often being the most frequent acute side effect. This study aimed to determine the efficacy of partially hydrolyzed guar gum (PHGG) usage in reducing radiotherapy-induced diarrhea and improving bacterial count, nutrition status, and quality of life (QoL) among cancer patients.
METHODS: Adult patients undergoing pelvic radiation were recruited and randomly assigned to receive supplementation of either 10 g of PHGG or placebo (maltodextrin) twice daily, 14 days prior and 14 days during pelvic radiation. Diarrhea frequency, fecal samples, nutrition status, and QoL were assessed at baseline and days 14, 28 (2 weeks after pelvic radiation), and 45 (at the completion of pelvic radiation, 2 weeks' postsupplementation).
RESULTS: A total of 30 patients (mean age 56.5 ± 10.8 years, 75% malnourished) participated. The mean of diarrhea frequency in the intervention group (IG) was higher compared with the control group (CG) from days 14 and 28 but reduced at day 45. There was a significant intervention effect after controlling for confounders (ie, baseline diarrhea, age, nutrition status) (P < .05). Bifidobacterium count increased by double among the IG at 14 days of PHGG supplementation, whereas such trend was not observed in the CG.
CONCLUSION: Supplementation of PHGG potentially increased the bifidobacterial count and seemed to have post-supplementation effects by reducing the frequency of diarrhea upon the completion of pelvic radiation treatment.
Identification of genetic and non-genetic risk factors for nasopharyngeal carcinoma in a Southeast Asian population

Nor Hashim NA, Ramzi NH, Velapasamy S, Alex L, Chahil JK, Lye SH, et al.

Asian Pac J Cancer Prev, 2012;13(12):6005-10.
PMID: 23464394

BACKGROUND: Nasopharyngeal carcinoma (NPC) is endemic in Southern Chinese and Southeast Asian populations. Geographical and ethnic clustering of the cancer is due to genetic, environmental, and lifestyle risk factors. This case-control study aimed to identify or confirm both genetic and non-genetic risk factors for NPC in one of the endemic countries, Malaysia.
MATERIALS AND METHOD: A panel of 768 single-nucleotide polymorphisms (SNPs) previously associated with various cancers and known non-genetic risk factors for NPC were selected and analyzed for their associations with NPC in a case-control study.
RESULTS: Statistical analysis identified 40 SNPs associated with NPC risk in our population, including 5 documented previously by genome-wide association studies (GWAS) and other case-control studies; the associations of the remaining 35 SNPs with NPC were novel. In addition, consistent with previous studies, exposure to occupational hazards, overconsumption of salt-cured foods, red meat, as well as low intake of fruits and vegetables were also associated with NPC risk.
CONCLUSIONS: In short, this study confirmed and/or identified genetic, environmental and dietary risk factors associated with NPC susceptibility in a Southeast Asian population.
Fulltext Genetic diversity of Eurycoma longifolia inferred from single nucleotide polymorphisms

Osman A, Jordan B, Lessard PA, Muhammad N, Haron MR, Riffin NM, et al.

Plant Physiol, 2003 Mar;131(3):1294-301.
PMID: 12644679 DOI: 10.1104/pp.012492

Eurycoma longifolia Jack. is a treelet that grows in the forests of Southeast Asia and is widely used throughout the region because of its reported medicinal properties. Widespread harvesting of wild-grown trees has led to rapid thinning of natural populations, causing a potential decrease in genetic diversity among E. longifolia. Suitable genetic markers would be very useful for propagation and breeding programs to support conservation of this species, although no such markers currently exist. To meet this need, we have applied a genome complexity reduction strategy to identify a series of single nucleotide polymorphisms (SNPs) within the genomes of several E. longifolia accessions. We have found that the occurrence of these SNPs reflects the geographic origins of individual plants and can distinguish different natural populations. This work demonstrates the rapid development of molecular genetic markers in species for which little or no genomic sequence information is available. The SNP markers that we have developed in this study will also be useful for identifying genetic fingerprints that correlate with other properties of E. longifolia, such as high regenerability or the appearance of bioactive metabolites.
Fulltext Role of genetic & environment risk factors in the aetiology of colorectal cancer in Malaysia

Ramzi NH, Chahil JK, Lye SH, Munretnam K, Sahadevappa KI, Velapasamy S, et al.

Indian J Med Res, 2014 Jun;139(6):873-82.
PMID: 25109722

Colorectal cancer (CRC) is second only to breast cancer as the leading cause of cancer-related deaths in Malaysia. In the Asia-Pacific area, it is the highest emerging gastrointestinal cancer. The aim of this study was to identify single nucleotide polymorphisms (SNPs) and environmental factors associated with CRC risk in Malaysia from a panel of cancer associated SNPs.