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All Journal Bioscientia Medicina : Journal of Biomedicine and Translational Research Bioscientia Medicina : Journal of Biomedicine and Translational Research
Norman Djamaludin
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Biochemistry, Genetics & Molecular Biology Immunology & microbiology Medicine & Pharmacology Neuroscience

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Targeting the TGF-β Pathway to Overcome Resistance to Immune Checkpoint Inhibitors in Microsatellite Stable Metastatic Colorectal Cancer: A Systematic Review and Pooled Analysis of Efficacy and Tumor Microenvironment Modulation Aprizal Satria; Norman Djamaludin; Yenny Dian Andayani; Mediarty Syahrir
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 9 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i9.1395

Abstract

Background: The clinical utility of immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC) is restricted to a minority of tumors with mismatch repair deficiency. The vast majority, classified as microsatellite stable (MSS), display profound resistance driven by an immunosuppressive tumor microenvironment (TME) orchestrated by transforming growth factor-β (TGF-β). This study aimed to synthesize the evidence for combining TGF-β pathway inhibitors with ICIs to reverse this resistance. Methods: A systematic search of PubMed, Embase, Cochrane Library, and major oncology conference abstracts was conducted through December 2024 for preclinical and clinical studies evaluating TGF-β inhibition combined with ICIs in CRC. Due to the non-randomized nature of the clinical evidence, a pooled analysis of the single-arm objective response rate (ORR) was performed using a random-effects model. Progression-free survival (PFS), duration of response (DoR), and TME modulation were synthesized narratively. Results: Seven studies (four preclinical, three early-phase clinical) met the inclusion criteria. In the pooled analysis of 218 patients with predominantly MSS-mCRC from three clinical trials, the combination therapy yielded a pooled ORR of 14.2% (95% Confidence Interval [CI]: 9.1% – 20.2%), with moderate heterogeneity (I² = 38%). This represents a clinically meaningful improvement over the expected <1% response rate to ICI monotherapy in this population. Narrative synthesis of survival data indicated a median PFS ranging from 2.5 to 3.7 months and a promising median DoR exceeding 10 months in responders. Preclinical data consistently demonstrated that combination therapy synergistically inhibited tumor growth by remodeling the TME, marked by increased CD8+ T-cell infiltration and reduced stromal fibrosis. Conclusion: This systematic review and pooled analysis provide the most current synthesis of evidence for targeting the TGF-β pathway in MSS-mCRC. While preliminary and based on early-phase trials, the data show that this combination strategy can induce durable responses in a subset of patients by promoting an inflamed TME. These findings strongly support the continued investigation of this approach in biomarker-driven, randomized controlled trials.
Targeting the TGF-β Pathway to Overcome Resistance to Immune Checkpoint Inhibitors in Microsatellite Stable Metastatic Colorectal Cancer: A Systematic Review and Pooled Analysis of Efficacy and Tumor Microenvironment Modulation Aprizal Satria; Norman Djamaludin; Yenny Dian Andayani; Mediarty Syahrir
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 9 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i9.1395

Abstract

Background: The clinical utility of immune checkpoint inhibitors (ICIs) in metastatic colorectal cancer (mCRC) is restricted to a minority of tumors with mismatch repair deficiency. The vast majority, classified as microsatellite stable (MSS), display profound resistance driven by an immunosuppressive tumor microenvironment (TME) orchestrated by transforming growth factor-β (TGF-β). This study aimed to synthesize the evidence for combining TGF-β pathway inhibitors with ICIs to reverse this resistance. Methods: A systematic search of PubMed, Embase, Cochrane Library, and major oncology conference abstracts was conducted through December 2024 for preclinical and clinical studies evaluating TGF-β inhibition combined with ICIs in CRC. Due to the non-randomized nature of the clinical evidence, a pooled analysis of the single-arm objective response rate (ORR) was performed using a random-effects model. Progression-free survival (PFS), duration of response (DoR), and TME modulation were synthesized narratively. Results: Seven studies (four preclinical, three early-phase clinical) met the inclusion criteria. In the pooled analysis of 218 patients with predominantly MSS-mCRC from three clinical trials, the combination therapy yielded a pooled ORR of 14.2% (95% Confidence Interval [CI]: 9.1% – 20.2%), with moderate heterogeneity (I² = 38%). This represents a clinically meaningful improvement over the expected <1% response rate to ICI monotherapy in this population. Narrative synthesis of survival data indicated a median PFS ranging from 2.5 to 3.7 months and a promising median DoR exceeding 10 months in responders. Preclinical data consistently demonstrated that combination therapy synergistically inhibited tumor growth by remodeling the TME, marked by increased CD8+ T-cell infiltration and reduced stromal fibrosis. Conclusion: This systematic review and pooled analysis provide the most current synthesis of evidence for targeting the TGF-β pathway in MSS-mCRC. While preliminary and based on early-phase trials, the data show that this combination strategy can induce durable responses in a subset of patients by promoting an inflamed TME. These findings strongly support the continued investigation of this approach in biomarker-driven, randomized controlled trials.
Premature Rupture of Membranes in a Pregnant Patient with Systemic Lupus Erythematosus and Lupus Carditis: A Case Report Wardani, Anisa Karamina; Nova Kurniati; Norman Djamaludin; Erwin Sukandi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 8 No. 10 (2024): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v8i10.1093

Abstract

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease associated with significant maternal and fetal risks, especially during pregnancy. Lupus carditis and premature rupture of membranes (PROM) pose additional challenges in managing such pregnancies. Case presentation: A 21-year-old woman with a history of SLE and lupus carditis presented at 34 weeks gestation with premature rupture of membranes. Her medical history was notable for regular follow-up and treatment for SLE manifestations, including mucocutaneous involvement and microcytic hypochromic anemia. Physical examination revealed characteristic signs of SLE, and echocardiography confirmed dilated cardiomyopathy. Following a multidisciplinary approach, a cesarean section was performed, resulting in the successful delivery of a healthy neonate. Conclusion: This case highlights the importance of a coordinated multidisciplinary approach in managing complex pregnancies involving SLE, lupus carditis, and PROM. Early diagnosis, close monitoring, and timely intervention are crucial for optimizing maternal and fetal outcomes in such cases.
Premature Rupture of Membranes in a Pregnant Patient with Systemic Lupus Erythematosus and Lupus Carditis: A Case Report Wardani, Anisa Karamina; Nova Kurniati; Norman Djamaludin; Erwin Sukandi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 8 No. 10 (2024): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v8i10.1093

Abstract

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease associated with significant maternal and fetal risks, especially during pregnancy. Lupus carditis and premature rupture of membranes (PROM) pose additional challenges in managing such pregnancies. Case presentation: A 21-year-old woman with a history of SLE and lupus carditis presented at 34 weeks gestation with premature rupture of membranes. Her medical history was notable for regular follow-up and treatment for SLE manifestations, including mucocutaneous involvement and microcytic hypochromic anemia. Physical examination revealed characteristic signs of SLE, and echocardiography confirmed dilated cardiomyopathy. Following a multidisciplinary approach, a cesarean section was performed, resulting in the successful delivery of a healthy neonate. Conclusion: This case highlights the importance of a coordinated multidisciplinary approach in managing complex pregnancies involving SLE, lupus carditis, and PROM. Early diagnosis, close monitoring, and timely intervention are crucial for optimizing maternal and fetal outcomes in such cases.
Co-Authors Aprizal Satria Erwin Sukandi Mediarty Syahrir Nova Kurniati Wardani, Anisa Karamina Yenny Dian Andayani