Displaying publications 1 - 20 of 57 in total

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  1. Ainuddin HA, Loh SY, Chinna K, Low WY, Roslani AC
    J Child Health Care, 2015 Jun;19(2):229-38.
    PMID: 24154841 DOI: 10.1177/1367493513504834
    Adolescence is the potential period for growth and optimal functioning, but developmental issues like time of transition from childhood to adulthood will create stress and affect the adolescent's quality of life (QOL). However, there is a lack of research tool for measuring adolescent's QOL in Malaysia. The aim of the study was to determine the validity and reliability of the self-report Malay version of the pediatric QOL (PedsQL™) 4.0 Generic Core Scales in assessing the QOL of Malaysian adolescents. A cross-sectional study design using the 23-item self-report Malay version of the PedsQL 4.0 Generic Core Scales was administered on a convenient cluster sampling (n = 297 adolescent) from a secondary school. The internal consistency reliability had Cronbach's α values ranging from .70 to .89. Factor analysis reported a six-factor structure via principal axis factor analysis. In conclusion, the self-report Malay version of the pediatric QOL 4.0 Generic Core Scales is a reliable and valid tool to measure the QOL of multiethnic Malaysian adolescents.
  2. Ainuddin HA, Loh SY, Low WY, Sapihis M, Roslani AC
    Asian Pac J Cancer Prev, 2012;13(12):6289-94.
    PMID: 23464447
    BACKGROUND: Research evidence suggests a debilitating impact of the diagnosis of cancer on the quality of life of the afflicted individuals, their spouses and their families. However, relatively few studies have been carried out on the impact on the QOL of adolescents living with parents diagnosed with cancer. This paper presents a sub- analysis on the impact of parental cancer (colorectal, breast and lung) on adolescents.

    MATERIALS AND METHODS: This is a cross-sectional study on adolescents aged 13-18 years old. Upon ethical clearance obtained from UMMC Medical Ethics Committee, patients with colorectal, breast or lung cancer and their adolescent children were recruited from the Clinical Oncology Unit of University of Malaya Medical Centre. Respondents who gave consent completed a demographic questionnaire and the Pediatric Quality of Life Inventory, via the post, email, home visit or meetings at the clinics.

    RESULTS: 95 adolescents from 50 families responded, giving a response rate of 88 percent. The adolescent's mean age was 16 years (ranging between 13-18 years). Adolescents with parental cancer had the lowest mean score in emotional functioning (p<0.05). Male adolescents had significantly higher quality of life overall and in physical functioning compared to female adolescents. Adolescents with a father with cancer had better school functioning compared to adolescents whose mothers had cancer. Families with household income of RM 5000 and above have significantly better quality of life compared to families with lower household income.

    CONCLUSIONS: Adolescent sons and daughters of parents with a cancer diagnosis show lowered QOL, particularly with reference to emotional functioning and school performance. Addressing the needs of this young group has been slow and warrants special attention. Revisiting the risk and resilience factors of adolescents might also inform tailored programs to address the needs of this neglected adolescent population.

  3. Arul M, Roslani AC, Cheah SH
    In Vitro Cell Dev Biol Anim, 2017 May;53(5):435-447.
    PMID: 28120247 DOI: 10.1007/s11626-016-0126-x
    Tumor heterogeneity may give rise to differential responses to chemotherapy drugs. Therefore, unraveling tumor heterogeneity has an implication for biomarker discovery and cancer therapeutics. To test this phenomenon, we investigated the differential responses of three secondary colorectal cancer cell lines of different origins (HCT116, HT29, and SW620 cells) and four novel primary cell lines obtained from different colorectal cancer patients to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) and explored the differences in gene expression among the primary cell lines in response to exposure to cytotoxic drugs. Cells were exposed to different doses of 5-FU and L-OHP separately or in combinations of equitoxic drug or equimolar drug ratios (median effect of Chou-Talalay principle). Cell viability was assessed using MTT assay and the respective IC50values were determined. Changes in gene expression in primary cell lines after exposure to the same drug doses were compared using real-time PCR array. The sensitivities (IC50) of different cell lines, both secondary and primary, to 5-FU and L-OHP were significantly different, whether in monotherapy or combined treatment. Primary cell lines needed higher doses to reach IC50. There were variations in gene expression among the primary cell lines of different chemosensitivities to the challenge of the same combined dose of 5-FU and L-OHP. The results confirm the heterogeneous nature of colorectal cancer cells from different patient tumors. Studies using primary cancer cells established from patient's tumors rather than secondary cell lines will more closely reflect the actual character of the disease.
  4. Arul M, Roslani AC, Ng CL, Cheah SH
    Cytotechnology, 2014 May;66(3):481-91.
    PMID: 23824584 DOI: 10.1007/s10616-013-9600-4
    There is increasing evidence that a tumour comprises of heterogeneous population of cells. Thus, studying homogenous cell lines in vitro may yield results that are not reflective of the true situation in a tumour and studying low passage cell lines maintained in a heterogeneous population before they transform away from the original state may provide a more complete picture of colorectal cancer. A method was developed to isolate and establish low passage colorectal cancer cell lines from tumour biopsies. The media contents, combination of antimicrobials and specimen collection and transport conditions employed, successfully eliminated microbial contamination which is frequently present in samples obtained from the gastrointestinal tract. A variety of growth forms indicating a heterogeneous mixture of cells was seen in the initial cultures. Using fluorescence immunocytochemistry, primary tumour cultures were shown to variably express selected tumour markers, carcinoembryonic antigen and C2 antigen. These low passage cell lines growing in a heterogeneous environment would more closely reflect the characteristics of the cells of the original tumour.
  5. Azzani M, Roslani AC, Su TT
    Support Care Cancer, 2015 Mar;23(3):889-98.
    PMID: 25337681 DOI: 10.1007/s00520-014-2474-y
    PURPOSE: The escalating health-care spending for cancer management has caused cancer patients to struggle further as a result of financial burden. This systematic review was carried out to investigate the prevalence of perceived financial hardship and associated factors among cancer patients and their families.

    METHODS: A systematic search for studies concerning the perception of financial burden among cancer patients and their families was conducted. Several electronic resources such as Medline, Elsevier (Science Direct), Web of Science, Embase, PubMed, CINAHL and Scopus (SciVerse) were searched. Additionally, manual search through indices citation was also thoroughly utilized. The main outcome of interest was the prevalence of perceived financial hardship among cancer patients and their families. Studies reported only the cost of cancer treatment and qualitative studies were excluded. Our search was limited to articles that were published from 2003 to 2013.

    RESULT: Ten studies were included in this review and with a majority originating from high-income countries. The prevalence of the financial burden perception was reported between 14.8 and 78.8 %. The most frequent and significant risk factor reported associated with the perception of financial difficulty was the households with low income. Discontinuation of treatment and poverty were conversely the important consequences of financial burden in cancer patients and their families.

    CONCLUSION: Evidently, cancer is a long-term illness that requires a high financial cost, and a significant number of cancer patients and families struggle with financial difficulty. Identifying such groups with a high risk of facing financial difficulty is a crucial measure to ensure safety nets are readily available for these targeted population.

  6. Azzani M, Roslani AC, Su TT
    Support Care Cancer, 2016 10;24(10):4423-32.
    PMID: 27225528 DOI: 10.1007/s00520-016-3283-2
    BACKGROUND: In Malaysia, the healthcare system consists of a government-run universal healthcare system and a co-existing private healthcare system. However, with high and ever rising healthcare spending on cancer management, cancer patients and their families are likely to become vulnerable to a healthcare-related financial burden. Moreover, they may have to reduce their working hours and lose income. To better understand this issue, this study aims to assess the financial burden of colorectal cancer patients and their families in the first year following diagnosis.

    METHODS: Data on patient costs were collected prospectively in the first year following diagnosis by using a self-administered questionnaire and telephone interviews at three time points for all four stages of colorectal cancer. The patient cost data consisted of direct out-of-pocket payments for medical-related expenses such as hospital stays, tests and treatment and for non-medical items such as travel and food associated with hospital visits. In addition, indirect cost data related to the loss of productivity of the patient and caregiver(s) was assessed. The patient's perceived level of financial difficulty and types of coping strategy were also explored.

    RESULT: The total 1-year patient cost (both direct and indirect) increased with the stage of colorectal cancer: RM 6544.5 (USD 2045.1) for stage I, RM 7790.1 (USD 2434.4) for stage II, RM 8799.1 (USD 2749.7) for stage III and RM 8638.2 (USD 2699.4) for stage IV. The majority of patients perceived paying for their healthcare as somewhat difficult. The most frequently used financial coping strategy was a combination of current income and savings.

    CONCLUSION: Despite the high subsidisation in public hospitals, the management of colorectal cancer imposes a substantial financial burden on patients and their families. Moreover, the majority of patients and their families perceive healthcare payments as difficult. Therefore, it is recommended that policy- and decision-makers should further consider some financial protection strategies and support for cancer treatment because cancer is a very costly and chronic disease.

  7. Azzani M, Yahya A, Roslani AC, Su TT
    Asia Pac J Public Health, 2017 Sep;29(6):485-494.
    PMID: 29019257 DOI: 10.1177/1010539517732224
    This study aimed to estimate the cost of colorectal cancer (CRC) management and to explore the prevalence and determinants of catastrophic health expenditure (CHE) among CRC patients and their families arising from the costs of CRC management. Data were collected prospectively from 138 CRC patients. Patients were interviewed by using a structured questionnaire at the time of the diagnosis, then at 6 months and 12 months following diagnosis. Simple descriptive methods and multivariate binary logistic regression were used in the analysis. The mean cost of managing CRC was RM8306.9 (US$2595.9), and 47.8% of patients' families experienced CHE. The main determinants of CHE were the economic status of the family and the likelihood of the patient undergoing surgery. The results of this study strongly suggest that stakeholders and policy makers should provide individuals with financial protection against the consequences of cancer, a costly illness that often requires prolonged treatment.
  8. Azzani M, Dahlui M, Ishak WZW, Roslani AC, Su TT
    Malays J Med Sci, 2019 Jan;26(1):73-86.
    PMID: 30914895 MyJurnal DOI: 10.21315/mjms2019.26.1.7
    Background: The incidence of colorectal cancer (CRC) is rapidly rising in several Asian countries, including Malaysia, but there is little data on health care provider costs in this region. The aim of this study was to estimate the cost of CRC management from the perspective of the health care provider, based on standard operating procedures.

    Methods: A combination of top-down approach and activity-based costing was applied. The standard operating procedure (SOP) for CRC was developed for each stage according to national data and guidelines at the University of Malaya Medical Centre (UMMC). The unit cost was calculated and incorporated into the treatment pathway in order to obtain the total cost of managing a single CRC patient according to the stage of illness. The cost data were represented by means and standard deviation and the results were demonstrated by tabulation. All cost data are presented in Malaysian Ringgit (RM). The cost difference between early stage (Stage I) and late stage (Stage II-IV) was analysed using independent t-test.

    Results: The cost per patient increased with stage of CRC, from RM13,672 (USD4,410.30) for stage I, to RM27,972 (USD9,023.20) for Stage IV. The early stage had statistically significant lower cost compared to late stage t(2) = -4.729, P = 0.042. The highest fraction of the cost was related to surgery for Stage I, but was superseded by oncology day care treatment for Stages II-IV. CRC is a costly illness. From a provider perspective, the highest cost was found in Stages III and IV. The early stages conserved more resources than did the advanced stages of cancer.

    Conclusion: Early diagnosis and management of CRC, therefore, not only affects oncologic prognosis, but has implications for health care costs. This adds further justification to develop and implement CRC screening programmes in Malaysia.

  9. Azzani M, Roslani AC, Su TT
    Malays J Med Sci, 2019 Jan;26(1):15-43.
    PMID: 30914891 MyJurnal DOI: 10.21315/mjms2019.26.1.3
    The World Health Organization estimates that annually 150 million people experience severe (catastrophic) financial difficulties as a result of healthcare payments. Therefore, a systematic review was carried out to identify the determinants of household catastrophic health expenditure (CHE) in low-to high-income countries around the world. Both electronic and manual searches were conducted. The main outcome of interest was the determinants of CHE due to healthcare payments. Thirty eight studies met the inclusion criteria for review. The analysis revealed that household economic status, incidence of hospitalisation, presence of an elderly or disabled household member in the family, and presence of a family member with a chronic illness were the common significant factors associated with household CHE. The crucial finding of the current study is that socioeconomic inequality plays an important role in the incidence of CHE all over the world, where low-income households are at high risk of financial hardship from healthcare payments. This suggests that healthcare financing policies should be revised in order to narrow the gap in socioeconomic inequality and social safety nets should be implemented and strengthened for people who have a high need for health care.
  10. Bobel MC, Al Hinai A, Roslani AC
    Clin Colon Rectal Surg, 2022 Sep;35(5):371-375.
    PMID: 36111081 DOI: 10.1055/s-0042-1746186
    Global surgery is a burgeoning area of global health. Surgeons can engage in one-or many-of the facets of global healthcare delivery: clinical care, capacity building, education, research, etc. Working in an increasingly global community, surgeons must be aware of the richness of cultural diversity at home and around the world such that they can provide culturally sensitive care. This chapter focuses on the most common way in which surgeons engage in global surgery: surgical short-term experiences in global health (STEGHs). Surgical STEGHs pose an intricate set of ethical dilemmas. As team leaders, surgeons must understand the community they intend to serve on these trips. Further, they should confirm that everyone who joins them is prepared to deliver care in a culturally sensitive and competent manner. Finally, surgeons must consider potential ethical dilemmas that may arise before, during, and after surgical STEGHs and have strategies to navigate them.
  11. Chan WK, Roslani AC, Law CW, Goh KL, Mahadeva S
    J Dig Dis, 2013 Dec;14(12):670-5.
    PMID: 23981291 DOI: 10.1111/1751-2980.12097
    To compare the outcomes and costs of endoluminal clipping and surgery in the management of iatrogenic colonic perforation.
  12. Cheng KP, Roslani AC, Sehha N, Kueh JH, Law CW, Chong HY, et al.
    Colorectal Dis, 2012 Jun;14(6):e346-51.
    PMID: 22568647 DOI: 10.1111/j.1463-1318.2012.02943.x
    Surgical site infection (SSI) remains a common postoperative morbidity, particularly in colorectal resections, and poses a significant financial burden to the healthcare system. The omission of mechanical bowel preparation, as is performed in enhanced recovery after surgery programmes, appears to further increase the incidence. Various wound protection methods have been devised to reduce the incidence of SSIs. However, there are few randomized controlled trials assessing their efficacy. The aim of this study is to investigate whether ALEXIS wound retractors with reinforced O-rings are superior to conventional wound protection methods in preventing SSIs in colorectal resections.
  13. Chong HY, Roslani AC, Law CW
    Med J Malaysia, 2013;68(1):30-3.
    PMID: 23466763 MyJurnal
    BACKGROUND: Screening for colorectal cancer (CRC) improves outcomes and reduces its incidence. However, population-based screening in Malaysia continues to be a challenge, in view of cost and limited availability of colonoscopic skills and facilities. Conventional qualitative faecal occult blood tests help to prioritize those who require earlier colonoscopies, but cannot distinguish between benign and malignant causes. Recently, quantitative immunochemical faecal occult blood tests (qFOBT) have demonstrated some discriminatory ability in distinguishing benign and malignant causes. We aim to assess feasibility of qFOBT as a tool for stratification of colonoscopic priority in asymptomatic patients.
    METHODS: A health awareness exhibition was held in a major shopping complex in Kuala Lumpur on 6 and 7 Feb 2010. All asymptomatic individuals> 40 years, and those < 40 with family history of CRC, were invited to participate. Eligible participants were given a questionnaire and screened using a qFOBT. A faecal haemoglobin level of 100 - 199 ng/mL was considered moderately positive, while a level of 200 ng/mL or more was strongly positive. Participants with a strongly positive qFOBT result were scheduled for a colonoscopy within the month, while those who were moderately positive were scheduled within 3 months.
    RESULTS: A total of 125 (82%) participants returned the qFOBT kit, of which 70 (56%) were male. The median age was 54 years. Majority of the participants were Chinese (60%), followed by Malay (25%), Indian (12%) and others (3%). Twelve (10%) participants were tested positive and were advised to undergo colonoscopy but 9 (75%) declined colonoscopy and further investigations citing lack of time as the reason. Of the 3 participants (all in the moderately positive group) who underwent colonoscopy, 2 had a family history of CRC. Colonoscopic findings revealed haemorrhoids in one participant and two participants had histologically proven benign sigmoid colonic polyps.
    CONCLUSION: The use of qFOBT as a tool to screen and prioritize asymptomatic patients for early colonoscopy in CRC screening is logistically feasible. However, in order for it to be effective, measures to improve compliance to colonoscopy need to be taken.
  14. Dejea CM, Wick EC, Hechenbleikner EM, White JR, Mark Welch JL, Rossetti BJ, et al.
    Proc Natl Acad Sci U S A, 2014 Dec 23;111(51):18321-6.
    PMID: 25489084 DOI: 10.1073/pnas.1406199111
    Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.
  15. Drewes JL, White JR, Dejea CM, Fathi P, Iyadorai T, Vadivelu J, et al.
    NPJ Biofilms Microbiomes, 2019 01 09;5(1):2.
    PMID: 30652010 DOI: 10.1038/s41522-018-0078-x
    [This corrects the article DOI: 10.1038/s41522-017-0040-3.].
  16. Drewes JL, White JR, Dejea CM, Fathi P, Iyadorai T, Vadivelu J, et al.
    PMID: 29214046 DOI: 10.1038/s41522-017-0040-3
    Colorectal cancer (CRC) remains the third most common cancer worldwide, with a growing incidence among young adults. Multiple studies have presented associations between the gut microbiome and CRC, suggesting a link with cancer risk. Although CRC microbiome studies continue to profile larger patient cohorts with increasingly economical and rapid DNA sequencing platforms, few common associations with CRC have been identified, in part due to limitations in taxonomic resolution and differences in analysis methodologies. Complementing these taxonomic studies is the newly recognized phenomenon that bacterial organization into biofilm structures in the mucus layer of the gut is a consistent feature of right-sided (proximal), but not left-sided (distal) colorectal cancer. In the present study, we performed 16S rRNA gene amplicon sequencing and biofilm quantification in a new cohort of patients from Malaysia, followed by a meta-analysis of eleven additional publicly available data sets on stool and tissue-based CRC microbiota using Resphera Insight, a high-resolution analytical tool for species-level characterization. Results from the Malaysian cohort and the expanded meta-analysis confirm that CRC tissues are enriched for invasive biofilms (particularly on right-sided tumors), a symbiont with capacity for tumorigenesis (Bacteroides fragilis), and oral pathogens including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus stomatis. Considered in aggregate, species from the Human Oral Microbiome Database are highly enriched in CRC. Although no detected microbial feature was universally present, their substantial overlap and combined prevalence supports a role for the gut microbiota in a significant percentage (>80%) of CRC cases.
  17. Housseau F, Wu S, Wick EC, Fan H, Wu X, Llosa NJ, et al.
    Cancer Res, 2016 04 15;76(8):2115-24.
    PMID: 26880802 DOI: 10.1158/0008-5472.CAN-15-0749
    IL17-producing Th17 cells, generated through a STAT3-dependent mechanism, have been shown to promote carcinogenesis in many systems, including microbe-driven colon cancer. Additional sources of IL17, such as γδ T cells, become available under inflammatory conditions, but their contributions to cancer development are unclear. In this study, we modeled Th17-driven colon tumorigenesis by colonizing Min(Ap) (c+/-) mice with the human gut bacterium, enterotoxigenic Bacteroides fragilis (ETBF), to investigate the link between inflammation and colorectal cancer. We found that ablating Th17 cells by knocking out Stat3 in CD4(+) T cells delayed tumorigenesis, but failed to suppress the eventual formation of colonic tumors. However, IL17 blockade significantly attenuated tumor formation, indicating a critical requirement for IL17 in tumorigenesis, but from a source other than Th17 cells. Notably, genetic ablation of γδ T cells in ETBF-colonized Th17-deficient Min mice prevented the late emergence of colonic tumors. Taken together, these findings support a redundant role for adaptive Th17 cell- and innate γδT17 cell-derived IL17 in bacteria-induced colon carcinogenesis, stressing the importance of therapeutically targeting the cytokine itself rather than its cellular sources. Cancer Res; 76(8); 2115-24. ©2016 AACR.
  18. Huh JW, Maeda K, Liu Z, Wang X, Roslani AC, Lee WY
    Ann Coloproctol, 2020 Apr;36(2):70-77.
    PMID: 32054250 DOI: 10.3393/ac.2020.01.19
    PURPOSE: Current acceptance of the watch-and-wait (W&W) approach by surgeons in Asia-Pacific countries is unknown. An international survey was performed to determine status of the W&W approach on behalf of the Asia-Pacific Federation of Coloproctology (APFCP).

    METHODS: Surgeons in the APFCP completed an Institutional Review Board-approved anonymous e-survey and/or printed letters (for China) containing 19 questions regarding nonsurgical close observation in patients who achieved clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT).

    RESULTS: Of the 417 responses, 80.8% (n = 337) supported the W&W approach and 65.5% (n = 273) treated patients who achieved cCR after nCRT. Importantly, 78% of participants (n = 326) preferred a selective W&W approach in patients with old age and medical comorbidities who achieved cCR. In regard to restaging methods after nCRT, the majority of respondents based their decision to use W&W on a combination of magnetic resonance imaging results (94.5%, n = 394) with other test results. For interval between nCRT completion and tumor response assessment, most participants used 8 weeks (n = 154, 36.9%), followed by 6 weeks (n = 127, 30.5%) and 4 weeks (n = 102, 24.5%). In response to the question of how often responders followed-up after W&W, the predominant period was every 3 months (209 participants, 50.1%) followed by every 2 months (75 participants, 18.0%). If local regrowth was found during follow-up, most participants (79.9%, n = 333) recommended radical surgery as an initial management.

    CONCLUSION: The W&W approach is supported by 80% of Asia-Pacific surgeons and is practiced at 65%, although heterogeneous hospital or society protocols are also observed. These results inform oncologists of future clinical study participation.

  19. Iyadorai T, Mariappan V, Vellasamy KM, Wanyiri JW, Roslani AC, Lee GK, et al.
    PLoS One, 2020;15(1):e0228217.
    PMID: 31990962 DOI: 10.1371/journal.pone.0228217
    Escherichia coli (E. coli) from the B2 phylogenetic group is implicated in colorectal cancer (CRC) as it possesses a genomic island, termed polyketide synthetase (pks), which codes for the synthesis of colibactin, a genotoxin that induces DNA damage, cell cycle arrest, mutations and chromosomal instability in eukaryotic cells. The aim of this study was to detect and compare the prevalence of E. coli expressing pks (pks+ E. coli) in CRC patients and healthy controls followed by investigating the virulence triggered by pks+ E. coli using an in-vitro model. Mucosal colon tissues were collected and processed to determine the presence of pks+ E. coli. Thereafter, primary colon epithelial (PCE) and colorectal carcinoma (HCT116) cell lines were used to detect cytopathic response to the isolated pks+ E. coli strains. Our results showed 16.7% and 4.3% of CRC and healthy controls, respectively were pks+ E. coli. Further, PCE displayed syncytia and cell swelling and HCT116 cells, megalocytosis, in response to treatment with the isolated pks+ E. coli strains. In conclusion, pks+ E. coli was more often isolated from tissue of CRC patients compared to healthy individuals, and our in-vitro assays suggest these isolated strains may be involved in the initiation and development of CRC.
  20. Kaur CP, Iyadorai T, Sears C, Roslani AC, Vadivelu J, Samudi C
    Microorganisms, 2023 Feb 09;11(2).
    PMID: 36838407 DOI: 10.3390/microorganisms11020443
    Klebsiella pneumoniae (K. pneumoniae) colonizes the human gut and is a causative factor of pyogenic liver abscess (PLA). Retrospective studies conducted on K. pneumoniae PLA patients revealed subsequent CRC development in later years of their life with increasing prevalence of these strains harbouring polyketide synthase (PKS) genes. To our knowledge there are no known studies directly implicating K. pneumoniae with CRC to date. Our aims are to characterize K. pneumoniae isolates from CRC patients and investigate its effects on cell proliferation in vitro. K. pneumoniae isolates were characterized by screening virulence genes including polyketide synthase (PKS), biofilm assay, antibiotic susceptibility, and string test to determine hypervirulent (hvKp) strains. Solubilised antigens of selected K. pneumoniae isolates were co-cultured with primary colon cell lines and CRC cell lines (Stage I-IV) for 48 h. The enhancement of proliferation was measured through MTT and ECIS assay. Twenty-five percent of K. pneumoniae isolates were PKS-positive out of which 50% were hvKp strains. The majority of the isolates were from the more virulent serotype of K1 (30%) and K2 (50%). PKS-positive K. pneumoniae isolates did not possess genes to confer carbapenem resistance but instead were more highly associated with siderophore genes (aerobactin, enterobactin, and yersiniabactin) and allantoin metabolism genes (allS, allS2). Cell proliferation in primary colon, SW1116 (Stage I), and SW480 (Stage II) CRC cell lines were enhanced when co-cultured with PKS-positive K. pneumoniae antigens. ECIS revealed enhanced cell proliferation upon recurrent antigen exposure. This demonstrates the possible role that PKS-positive K. pneumoniae has in exacerbating CRC progression.
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