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PENGARUH OVARIEKTOMI TERHADAP KADAR VEGF,TGF-β, IGF, DAN CA15-3 PADA PASIEN KANKER PAYUDARA STADIUM LANJUT USIA MUDA Rini Suswita; Wirsma Arif; Edison Edison; Zelly Diarofinda
Majalah Kedokteran Andalas Vol 38, No 3 (2015): Published in December 2015
Publisher : Faculty of Medicine, Universitas Andalas

AbstrakKanker payudara stadium lanjut pada usia muda dikaitkan dengan gambaran klinis, patologis dan prognosis yang lebih buruk dibanding usia tua. Ovariektomi merupakan terapi paliatif yang efektif pada pasien ini, dengan menurunkan kadar estradiol yang akan mempengaruhi gen yang terlibat dalam proses proliferasi, diferensiasi, metastasis, angiogenesis, invasi, dan apoptosis. Penelitian ini bertujuan untuk mengetahui pengaruh ovariektomi terhadap kadar VEGF, TGF β, IGF dan CA15-3 pada pasien kanker payudara stadium lanjut usia muda. Penelitian ini menggunakan desain pre dan post test pada 12 pasien kanker payudara stadium lanjut usia muda sebagai subyek penelitian. Pemeriksaan kadar VEGF, TGF β, IGF dan CA 15-3 dilakukan sebelum dan tiga bulan sesudah pasien dilakukan tindakan ovariektomi dengan menggunakan teknik ELISA, kemudian dilakukan analisis statistik dengan uji non parametrik. Penelitian menemukan peningkatan kadar VEGF, TGF β, IGF dan CA 15-3 dan menurun sesudah dilakukan ovariektomi. Analisis statistik menunjukkan pengaruh ovariektomi yang bermakna terhadap penurunan kadar VEGF (p=0,023), TGF β (p=0,02), dan CA 15-3 (p=0,002), tetapi tidak berpengaruh terhadap kadar IGF(p=875). Ovariektomi dapat menurunkan kadar VEGF, TGF β dan CA 15-3 serum, sehingga dapat dipertimbangkan sebagai terapi pilihan pada kanker payudara stadium lanjut usia muda.AbstractAdvanced breast cancer in young age is associated with worse clinical features, pathology and prognosis than old age. Oophorectomy may be an effective palliative therapy in these patients, by decreasing estradiol concentration which will affect genes involved in proliferation, differentiation, metastasis, angiogenesis, invasion, and apoptosis. This research aimed at examining the effect of oophorectomy on the levels of VEGF, TGF-β, IGF and CA15-3 in patients with advanced breast cancer in young age. This study used a pre and post test design in twelve patients with advanced breast cancer in young age. The level of VEGF, TGF-β, IGF and CA 15-3 was measured before and three months after oophorectomy using the ELISA technique. Data was analyzed with non-parametric test. Of the twelve patients studied, there were increased levels of VEGF, TGF-β, IGF, and CA 15-3 before oophorectomy and there was a decrease after oophorectomy performed. Statistical analysis showed that oophorectomy significantly decreased levels of VEGF (p = 0,023), TGF-β (p = 0,02), and CA 15-3 (p = 0,002), but no significant effect on the decrease in IGF levels (p = 0,875 ). Oophorectomy reduces levels of VEGF, TGF β and CA 15-3 serum significantly in the first three months of observation. Thus, it could be considered for the management of advanced breast cancer in young age.

Lactococcus Lactis D4 Starter Fermented Milk’s Effect on Liver Function of Obstructive Jaundice Model Hannan Khairu Anami; M. Iqbal Rivai; Avit Suchitra; Irwan Irwan; Rini Suswita; Juni Mitra
Indonesian Journal of Multidisciplinary Science Vol. 2 No. 5 (2023): Indonesian Journal of Multidisciplinary Science
Publisher : International Journal Labs

Obstructive jaundice can cause liver function damage which exacerbates patient morbidity and mortality. Fermented milk starter Lactococcus Lactis D4 derived from dadih is a probiotic that has the potential to improve liver function through the enterohepatic pathway. The research would like to determine the effect of Lactococcus Lactis D4 starter fermented milk on liver function of obstructive jaundice. This study was an experimental study with a post test only randomized control group design in 3 groups of Rattus Novergicus strain Wistar rats with obstructive jaundice model which got ligation of biliary ducts and given Lactococcus lactis D4 starter fermented milk for 7 days. Liver function was assessed by looking at the levels of total bilirubin, SGOT, SGPT, ALP, and GGT in each treatment group. Administration of Lactococcus Lactis D4 starter fermented milk caused a decrease in SGOT levels (LDB + BAL vs LDB: 51.12 ± 1.77 U/L vs 64.63 ± 0.10 U/L, p<0.05) and SGPT (LDB + LAB vs LDB: 60.60±0.85 U/L vs 67.77±2.60 U/L, p<0.05) which was significant. However, there was no significant effect on total bilirubin levels (LDB + BAL vs LDB: 3.21±0.11 mg/dl vs 3.18±0.10 mg/dl, p>0.05), ALP (LDB + LAB vs LDB: 108.20 ± 2.78 U/L vs 115.38 ± 5.08 U/L, p>0.05), and GGT (LDB + LAB vs LDB: 12.57 ± 0.45 U/L vs 12.78±0.31 U/L, p>0.05). Lactococus Lactis D4 starter fermented milk can improve liver function which is indicated by a decrease in SGOT and SGPT levels in experimental animals.

Role Of Endoscopy To Reduce Extreme Hyperbilirubinemia In Lemmel Syndrome : A Case Report Rini Suswita
Majalah Kedokteran Andalas Vol 46, No 4 (2023): Online Juli 2023
Publisher : Faculty of Medicine, Universitas Andalas

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.25077/mka.v46.i4.p730-735.2023

Duodenal diverticulum is a false diverticulum which is generally asymptomatic, frequently founded incidentally at endoscopy and 22% at autopsy. One to five percent of duodenal diverticulum have complications such as bilio-pancreatic complications. Lemmel syndrome is a complication of bilio-pancreatic characterized by jaundice, increased levels of bilirubin, liver and pancreatic enzymes. Reported a male patient, 72 years old, he complained abdominal pain in the right upper quadrant, yellow eyes and body, and dark tea-colored urine. Abdominal pain with Visual Analog Scale (VAS) value between 6 to 7. Blood test resulted prolonged APTT 37", PT 17.7", INR 1.66, increased in total bilirubin 26.0 mg/dL with a ratio of direct and indirect bilirubin was 15.0 mg/dL and 11.0 mg/dL consecutively, hyponatremia 133 mmol/L, and hypokalemia 5.2 mmol/L. Abdominal CT scan examination showed compression of the distal bile duct (common bile duct) and dilatation of the proximal bile duct, both intra and extra-hepatic bile ducts. ERCP with endoscopic sphincterotomy and biliary stent placement can be an option for drainage and decompression of the biliary tract to prevent further complications to severe hyperbilirubinemia and the effects of biliary tract obstruction.

Exploring the Therapeutic Landscape: A Systematic Review on the Anti-inflammatory Effects of Probiotics in Colitis-associated Colorectal Cancer Rini Suswita
Majalah Kedokteran Andalas Vol 46, No 10 (2024): Supplementary April 2024
Publisher : Faculty of Medicine, Universitas Andalas

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.25077/mka.v46.i10.p1635-1656.2024

Background: Cancer is the second-leading cause of mortality worldwide. The inflammatory process has a well-known correlation with colorectal cancer, with chronic inflammation leading to malignancy. Long-term colitis disease has a 2-3-fold higher risk of colorectal cancer. Inflammation is involved in the development and progression of colitis-associated colorectal cancer (CAC), with molecular mediators and cytokines contributing to carcinogenesis. A diet of dairy products, such as probiotics, has been linked to a decrease in the incidence of colorectal cancer. Probiotics, known for their ability to modulate gut microbiota and immune responses, could potentially disrupt the inflammatory microenvironment implicated in the progression of colorectal cancer. Methods: We searched three databases: PubMed, ScienceDirect, and Wiley Online Library, using the respective keywords. A total of 248 studies were screened for eligibility, and nine studies eventually met the criteria and were reviewed. The SYRCLE RoB Tools were used to assess the risk of bias in the included studies.Results: The present evidence showed that treatment with probiotics was considered to be able to ameliorate the inflammation occurring in the CAC progression, as reflected in the severity of clinical signs, the expression of inflammatory markers, and the regulation of some pathways.

Role Of Endoscopy To Reduce Extreme Hyperbilirubinemia In Lemmel Syndrome : A Case Report Suswita, Rini
Majalah Kedokteran Andalas Vol. 46 No. 3 (2023): Online Juli 2023
Publisher : Faculty of Medicine, Universitas Andalas

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.25077/mka.v46.i4.p730-735.2023

Duodenal diverticulum is a false diverticulum which is generally asymptomatic, frequently founded incidentally at endoscopy and 22% at autopsy. One to five percent of duodenal diverticulum have complications such as bilio-pancreatic complications. Lemmel syndrome is a complication of bilio-pancreatic characterized by jaundice, increased levels of bilirubin, liver and pancreatic enzymes. Reported a male patient, 72 years old, he complained abdominal pain in the right upper quadrant, yellow eyes and body, and dark tea-colored urine. Abdominal pain with Visual Analog Scale (VAS) value between 6 to 7. Blood test resulted prolonged APTT 37", PT 17.7", INR 1.66, increased in total bilirubin 26.0 mg/dL with a ratio of direct and indirect bilirubin was 15.0 mg/dL and 11.0 mg/dL consecutively, hyponatremia 133 mmol/L, and hypokalemia 5.2 mmol/L. Abdominal CT scan examination showed compression of the distal bile duct (common bile duct) and dilatation of the proximal bile duct, both intra and extra-hepatic bile ducts. ERCP with endoscopic sphincterotomy and biliary stent placement can be an option for drainage and decompression of the biliary tract to prevent further complications to severe hyperbilirubinemia and the effects of biliary tract obstruction.

Exploring the Therapeutic Landscape: A Systematic Review on the Anti-inflammatory Effects of Probiotics in Colitis-associated Colorectal Cancer Suswita, Rini; Alvarino; Eryati Darwin; Jamsari
Majalah Kedokteran Andalas Vol. 47 No. 3 (2024): MKA July 2024
Publisher : Faculty of Medicine, Universitas Andalas

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.25077/mka.v47.i3.p341-361.2024

Background: Colorectal cancer is closely linked to chronic inflammation; long-standing colitis confers a 2–3-fold higher risk. Modulating the gut–immune axis with probiotics may attenuate the inflammatory microenvironment of colitis-associated colorectal cancer (CAC). Objective:To evaluate the anti-inflammatory effects of probiotics in CAC animal models. Methods: We searched PubMed, ScienceDirect, and Wiley Online Library; 248 records were screened and 9 studies met inclusion. Risk of bias was appraised using SYRCLE RoB. Results: Probiotic treatment consistently reduced clinical severity, down-regulated inflammatory markers, and modulated key signaling pathways in CAC models. Nonetheless, evidence was heterogeneous, sample sizes were small, and dosing, strains, and formulations varied; safety reporting was limited. Conclusions: Probiotics show promise as anti-inflammatory adjuncts in CAC based on animal studies. Rigorous, standardized preclinical work and well-designed trials are needed to define optimal strains, dosing, and formulations, and to confirm efficacy and safety for translation.

Lactococcus lactis D4 Has Potential Effect to Alleviate Inflammation and Reverse Dysbiosis in Colitis Rat Model Suswita, Rini; Alvarino, Alvarino; Darwin, Eryati; Jamsari, Jamsari
The Indonesian Biomedical Journal Vol 16, No 2 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i2.2970

BACKGROUND: Inflammatory bowel disease (IBD) is a prevalent chronic inflammatory disorder of the gastrointestinal tract that may lead to colorectal cancer if untreated. Several medications for IBD have adverse side effects. Thus, there are high interest for searching alternative treatment to treat IBD. Lactococcus lactis D4 isolated from dadih, a traditional fermented buffalo milk product, was investigated for the effect on gut inflammation and microbial composition in the colitis rat model.METHODS: Eighteen male Sprague-Dawley rats were divided into three groups; control rats, colitis-induced rats, and colitis-induced rats treated with L. lactis D4 isolate. The control group received water, while the colitis-induced rats were given azoxymethane (AOM) and dextran sodium sulphate (DSS). Rats’ feces were collected for the analysis of gut microbiota diversity by next-generation sequencing and for the measurement of transforming growth factor (TGF)-β, nuclear factor kappa-B (NF-κB), interleukin (IL)-6, and tumor necrosis factor (TNF)-α colonic expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).RESULTS: L. lactis D4 administration was able to reduce inflammation in colitis by decreasing IL-6 expression (0.87 vs. 0.73), while expression of TGF-β, NF-κB, and TNF-α were increased compared to the model group, suggesting a complex immunomodulatory effect. Gut microbiota sequencing revealed a similarity between the control and treatment groups, suggesting L. lactis D4 has great potential to ameliorate gut microbiota dysbiosis in colitis rats.CONCLUSION: L. lactis D4 has a beneficial effect in decreasing pro-inflammatory cytokines and is able to reserve dysbiosis in colitis rat model. Thus, L. lactis D4 might be used as a therapeutic agent for IBD.KEYWORDS: colitis, gut microbiota, inflammation, inflammatory bowel disease, Lactococcus lactis D4, probiotic, proinflammatory cytokines

Lactococcus lactis D4 Restores Gut Microbiota Balance in Azoxymethane and Dextran Sulfate Sodium-induced Colorectal Cancer Rat Model Suswita, Rini; Rivai, Muhammad Iqbal; Iqbal, Muhammad; Irwan, Irwan; Suchitra, Avit
The Indonesian Biomedical Journal Vol 16, No 6 (2024)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v16i6.3311

BACKGROUND: Gut microbiota plays a crucial role in the initiation and progression of colorectal cancer (CRC), with various bacterial species including Lactococcus lactis implicated in this process. However, there is a lack of studies reporting the specific effects of L. lactis on microbiota balance in the context of CRC, especially strain D4. Therefore, this study was conducted to evaluate the effect of L. lactis D4 administration on gut microbiota balance in a rat model of CRC.METHODS: This experimental study involved Sprague Dawley rats that were separated into untreated control (CO group), CRC-induced (CA group), and L. lactis D4-treated CRC-induced (LLD group). The CRC induction was performed by giving azoxymethane (AOM) and dextran sulfate sodium (DDS). Gut microbiota profile was analyzed using next generation sequencing (NGS), and microbial community dynamics were assessed through alpha and beta diversity metrics.RESULTS: L. lactis D4 restored gut microbiota balance by regulating Firmicutes/Bacteroidota ratio, and changing the microbiota composition by increasing the number of bacteria from the phylum Actinobacteria and decreasing bacteria from the phylum Bacteroidota and Proteobacteria. Alpha diversity was reduced in the LLD group, suggesting a decreased bacterial diversity post-treatment, but more closely aligned with the CO group than the CA group. Beta diversity analysis showed that the microbial composition of the treated group was similar to the CO group, while the CA group exhibited a distinct microbiota profile, characterized by higher abundance of pathogenic bacteria and reducing beneficial microbial species.CONCLUSION: L. lactis D4 administration effectively modulates gut microbiota in CRC model, enhancing the presence of beneficial bacteria from the Firmicutes and Bacteroidota phylum while suppressing pathogenic species from the Proteobacteria phylum.KEYWORDS: colorectal cancer, gut microbiota, next generation sequencing, Lactococcus lactis D4

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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