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Synergistic Attenuation of the TNF-α/NF-κB Inflammatory Axis in Colorectal Carcinogenesis: Lactococcus lactis D4 as a Mucosal-Protective Adjuvant to Capecitabine Leonard Khriestsandi Saleh; M Iqbal Rivai; Rini Suswita; Irwan; Avit Suchitra
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 4 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i4.1571

Background: Capecitabine serves as a standard chemotherapeutic agent for colorectal cancer, but its clinical efficacy is frequently hindered by severe gastrointestinal toxicity and incomplete suppression of the inflammatory tumor microenvironment. We evaluated the synergistic potential of Lactococcus lactis D4, a probiotic strain isolated from traditional fermented buffalo milk, as an immunonutritional adjuvant to Capecitabine in a 1,2-dimethylhydrazine-induced colorectal cancer rat model. Methods: Sprague-Dawley rats were maintained on a standardized AIN-93G diet and induced with 1,2-dimethylhydrazine. Animals were randomized into Negative Control, Cancer Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Treatments were administered for 14 days. We assessed cachexia, macroscopic microadenoma multiplicity, and TNF-α expression utilizing immunohistochemistry. Synergy was mathematically validated using the Coefficient of Drug Interaction. Results: The Combination group significantly prevented chemotherapy-induced cachexia, demonstrating a 2.1% weight gain compared to a 4.5% weight loss in the Capecitabine monotherapy group (p < 0.05). Macroscopic microadenomas were rapidly reduced in the combination group. Furthermore, the combination therapy synergistically suppressed colonic TNF-α protein expression (Coefficient of Drug Interaction = 0.83). Additionally, L. lactis D4 entirely mitigated capecitabine-induced mucositis. Conclusion: L. lactis D4 functions as a highly potent adjuvant to Capecitabine. It prevents cachexia, protects mucosal architecture, and exerts a mathematically proven synergistic suppression of the TNF-α inflammatory axis.

Association of Carcinoembryonic Antigen, Hemoglobin, and Neutrophil to Lymphocyte Ratio with Colorectal Cancer Histopathological Grade in West Sumatra, Indonesia Muhammad Zidane Innanda; Dwi Yulia; Avit Suchitra; Wirsma Arif Harahap; Rikarni Rikarni; Eka Nofita
Jurnal Kesehatan Vol 17 No 1 (2026): Jurnal Kesehatan
Publisher : Poltekkes Kemenkes Tanjung Karang

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.26630/jk.v17i1.5584

Colorectal cancer is a global health issue with a significant incidence and mortality rate. Identifying clinical characteristics using tumor biomarkers and hematological parameters is a crucial aspect in evaluating tumor cell differentiation grade. This study aims to determine the characteristics of Carcinoembryonic Antigen (CEA) levels, hemoglobin, and Neutrophil to Lymphocyte Ratio (NLR) values as indicators of histopathological differentiation grade in colorectal cancer patients. This was an observational, analytic study with a retrospective design, using medical record data from patients at Dr. M. Djamil General Hospital in Padang, from January 2023 to December 2024. A total of 154 patients meeting the inclusion and exclusion criteria were selected using a total sampling technique. Data were analyzed using statistical tests to assess the significance of the relationship between variables. The patient distribution showed a higher prevalence of females (55.8%), and more than half (62.3%) were aged 50 years or older. The histopathological profile was predominantly low grade (81.2%). Statistical test results showed a significant association between CEA levels and histopathological differentiation grade (p=0.017). However, no statistically significant association was found between hemoglobin levels (p=0.822) or NLR values (p=0.303) and histopathological differentiation grade. There is a potential association between CEA levels and histopathological differentiation grade, whereas hemoglobin levels and NLR values did not show a significant association. CEA levels can serve as a potential indicator in predicting tumor differentiation grade in colorectal cancer patients.

Evaluating the Indigenous Probiotic Lactococcus lactis D4 as an Adjuvant to Capecitabine: Modulation of NF-κB in a Colorectal Carcinogenesis Model Arli Suryawinata; M Iqbal Rivai; Rini Suswita; Irwan; Avit Suchitra; Raflis Rustam
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i5.1572

Background: Chronic inflammation driven by the nuclear factor kappa-B (NF-κB) signaling pathway is a fundamental driver of colorectal cancer (CRC) pathogenesis, promoting tumor survival, mucosal proliferation, and profound chemoresistance. Capecitabine is a standard first-line fluoropyrimidine chemotherapy; however, its clinical utility is frequently compromised by dose-limiting toxicities and the activation of inflammatory feedback loops. Lactococcus lactis D4, a novel probiotic strain isolated from traditional Indonesian fermented buffalo milk (dadih), possesses well-documented immunomodulatory properties. Methods: A randomized controlled experimental study was conducted utilizing male Sprague-Dawley rats (n=37). Colorectal carcinogenesis was chemically induced via intraperitoneal administration of 1,2-dimethylhydrazine (DMH). Following strict histopathological confirmation of malignancy, the cohort was randomized into five distinct groups: Negative Control, Positive Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Interventions were administered daily for 14 days. Outcomes included NF-κB protein expression assessed via immunohistochemistry (IHC) and targeted gene expression quantification via RT-qPCR. Results: Immunohistochemical analysis demonstrated that the positive control group exhibited significantly elevated NF-κB protein expression (35.87 ± 13.53%). Capecitabine monotherapy significantly reduced this expression to 16.07 ± 3.79% (p=0.003). The Combination therapy achieved a profound reduction in NF-κB protein expression down to 12.99 ± 4.92%; however, this was not statistically superior to Capecitabine alone (p=1.000). Conversely, RT-qPCR analysis revealed no statistically significant difference in NF-κB mRNA levels among the experimental groups (p=0.094). Conclusion: The combination of L. lactis D4 and Capecitabine effectively reduces NF-κB protein expression in a preclinical CRC model, achieving suppression levels comparable to primary chemotherapy. The distinct discordance between the significant protein suppression and the sustained mRNA expression levels suggests potential post-transcriptional or post-translational regulatory mechanisms that warrant further targeted molecular investigation.

GAMBARAN PARASIT INTESTINAL PADA PASIEN KANKER KOLOREKTAL DI RSUP DR M DJAMIL PADANG TAHUN 2023 Nurul Arbaniah; Nuzulia Irawati; Firdawati; Selfi Renita Rusjdi; Avit Suchitra; Gusti Revilla
SINERGI : Jurnal Riset Ilmiah Vol. 3 No. 6 (2026): SINERGI : Jurnal Riset Ilmiah, Juni 2026
Publisher : Lembaga Pendidikan dan Penelitian Manggala Institute

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.62335/sinergi.v3i6.2684

Colorectal cancer is the third most common malignancy in the world, disturbing normal cell control and mechanism and damaging immune system, therefore the susceptibility to parasitic infection is increasing. The aim of this study was to determine the incidence of intestinal parasitic infections in colorectal cancer patients at RSUP Dr. M. Djamil Padang. This is a categorical descriptive study from primary data with a total sample of 65 colorectal cancer patients using consecutive sampling technique. This research uses univariate analysis and is presented in the form of a frequency distribution table. The results of the study showed that intestinal parasitic infections in colorectal cancer patients amounted to 47,7% (31/65) with intestinal parasites found Cryptosporidium sp. of 61,9% (26/42) and Blastocystis sp. 30,9% (13/42). Intestinal parasitic infections were higher in the age group of <40 years by 80% (12/31) and higher in male patients by 54,8% (17/31). The most common type of infection is single infection, amounting to 71% (22/31). Incidence of intestinal parasitic infections is quite high in colorectal cancer patients at RSUP Dr. M. Djamil Padang. Colorectal cancer patients need to be screened and considered given antiparasitic drugs as well as education about preventing diseases caused by intestinal parasites

Synergistic Attenuation of the TNF-α/NF-κB Inflammatory Axis in Colorectal Carcinogenesis: Lactococcus lactis D4 as a Mucosal-Protective Adjuvant to Capecitabine Leonard Khriestsandi Saleh; M Iqbal Rivai; Rini Suswita; Irwan; Avit Suchitra
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 4 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i4.1571

Background: Capecitabine serves as a standard chemotherapeutic agent for colorectal cancer, but its clinical efficacy is frequently hindered by severe gastrointestinal toxicity and incomplete suppression of the inflammatory tumor microenvironment. We evaluated the synergistic potential of Lactococcus lactis D4, a probiotic strain isolated from traditional fermented buffalo milk, as an immunonutritional adjuvant to Capecitabine in a 1,2-dimethylhydrazine-induced colorectal cancer rat model. Methods: Sprague-Dawley rats were maintained on a standardized AIN-93G diet and induced with 1,2-dimethylhydrazine. Animals were randomized into Negative Control, Cancer Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Treatments were administered for 14 days. We assessed cachexia, macroscopic microadenoma multiplicity, and TNF-α expression utilizing immunohistochemistry. Synergy was mathematically validated using the Coefficient of Drug Interaction. Results: The Combination group significantly prevented chemotherapy-induced cachexia, demonstrating a 2.1% weight gain compared to a 4.5% weight loss in the Capecitabine monotherapy group (p < 0.05). Macroscopic microadenomas were rapidly reduced in the combination group. Furthermore, the combination therapy synergistically suppressed colonic TNF-α protein expression (Coefficient of Drug Interaction = 0.83). Additionally, L. lactis D4 entirely mitigated capecitabine-induced mucositis. Conclusion: L. lactis D4 functions as a highly potent adjuvant to Capecitabine. It prevents cachexia, protects mucosal architecture, and exerts a mathematically proven synergistic suppression of the TNF-α inflammatory axis.

Evaluating the Indigenous Probiotic Lactococcus lactis D4 as an Adjuvant to Capecitabine: Modulation of NF-κB in a Colorectal Carcinogenesis Model Arli Suryawinata; M Iqbal Rivai; Rini Suswita; Irwan; Avit Suchitra; Raflis Rustam
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i5.1572

Background: Chronic inflammation driven by the nuclear factor kappa-B (NF-κB) signaling pathway is a fundamental driver of colorectal cancer (CRC) pathogenesis, promoting tumor survival, mucosal proliferation, and profound chemoresistance. Capecitabine is a standard first-line fluoropyrimidine chemotherapy; however, its clinical utility is frequently compromised by dose-limiting toxicities and the activation of inflammatory feedback loops. Lactococcus lactis D4, a novel probiotic strain isolated from traditional Indonesian fermented buffalo milk (dadih), possesses well-documented immunomodulatory properties. Methods: A randomized controlled experimental study was conducted utilizing male Sprague-Dawley rats (n=37). Colorectal carcinogenesis was chemically induced via intraperitoneal administration of 1,2-dimethylhydrazine (DMH). Following strict histopathological confirmation of malignancy, the cohort was randomized into five distinct groups: Negative Control, Positive Control, L. lactis D4 monotherapy, Capecitabine monotherapy, and Combination therapy. Interventions were administered daily for 14 days. Outcomes included NF-κB protein expression assessed via immunohistochemistry (IHC) and targeted gene expression quantification via RT-qPCR. Results: Immunohistochemical analysis demonstrated that the positive control group exhibited significantly elevated NF-κB protein expression (35.87 ± 13.53%). Capecitabine monotherapy significantly reduced this expression to 16.07 ± 3.79% (p=0.003). The Combination therapy achieved a profound reduction in NF-κB protein expression down to 12.99 ± 4.92%; however, this was not statistically superior to Capecitabine alone (p=1.000). Conversely, RT-qPCR analysis revealed no statistically significant difference in NF-κB mRNA levels among the experimental groups (p=0.094). Conclusion: The combination of L. lactis D4 and Capecitabine effectively reduces NF-κB protein expression in a preclinical CRC model, achieving suppression levels comparable to primary chemotherapy. The distinct discordance between the significant protein suppression and the sustained mRNA expression levels suggests potential post-transcriptional or post-translational regulatory mechanisms that warrant further targeted molecular investigation.

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