Asian Pacific Journal of Cancer Biology

The Relationship Between Kirsten Rat Sarcoma Mutations and Mismatch Repair Status in Colorectal Cancer Patients: A Preliminary Study

Mon, 14 Jul 2025 04:51:49 +0000

Background: Chromosomal instability (CIN) is a key pathway in colorectal cancer (CRC) tumorigenesis, occurring in 80%-85% of cases and leading to aneuploidy. CIN tumors often harbor mutations in APC, KRAS, and TP53, which drive tumor progression. Another crucial pathway, microsatellite instability (MSI), results from DNA mismatch repair (MMR) defects, leading to a hypermutable phenotype. MSI-CRC has distinct clinicopathologic features and a better prognosis than proficient MMR (pMMR) CRC. KRAS mutations, found in approximately 40% of CRC cases, drive tumor progression via the RAS/RAF/MAPK pathway. This study investigates the relationship between KRAS mutations and MMR status in CRC patients.

Methods: A preliminary cross-sectional study was conducted on CRC patients. KRAS mutations were analyzed using PCR, while MMR status was determined via immunohistochemistry and microsatellite testing. Clinical variables, including cancer stage, tumor category, and location, were analyzed.

Results: Among 55 patients, 91.3% had pMMR and 8.7% had deficient MMR (dMMR). KRAS mutations were more frequent in pMMR patients (80% of cases). Patients with pMMR and KRAS mutations exhibited aggressive tumors but responded to conventional therapy, whereas dMMR patients with KRAS mutations showed complex molecular profiles, potentially benefiting from immunotherapy.

Conclusion: KRAS mutations are primarily associated with pMMR in CRC, indicating distinct molecular pathways. Personalized treatment strategies should consider MMR status and KRAS mutations to optimize therapeutic outcomes. Further research is needed to explore their clinical implications.

Comparative Efficacy of Prostate Tumor Induction Methods in Wistar Rats

Mon, 14 Jul 2025 04:54:26 +0000

Objectives: This study aims to evaluate and compare the efficacy of three methods for inducing prostate tumors in male Wistar rats: hormonal induction using testosterone propionate, chemical induction with cadmium chloride, and a combination of both agents. The research seeks to enhance understanding of the interactions between environmental and hormonal factors in prostate cancer development.

Materials and Methods: Twenty-five male Wistar rats (180-220 grams) were randomly assigned to five groups: a control group (no induction), a low-dose cadmium chloride group (1 mg/kg), a high-dose cadmium chloride group (2 mg/kg), a testosterone propionate group (5 mg/kg), and a combination group (1 mg/kg cadmium chloride + 5 mg/kg testosterone). Each treatment was administered over four weeks, followed by a four-week observation period. Histopathological analyses were conducted on prostate tissues using Hematoxylin and Eosin (H&E) staining to assess tumor characteristics and progression.

Results: Histopathological examination revealed that the control group exhibited normal prostate architecture. The low-dose cadmium chloride group showed mild hyperplasia, while the high-dose group displayed significant dysplastic changes. The testosterone propionate group demonstrated hyperplastic and pleomorphic epithelium, indicative of early tumorigenesis. The combination group exhibited the most aggressive tumors, characterized by severely dysplastic epithelium and stromal invasion. Survival rates were notably lower in the combination group, indicating increased health risks associated with dual exposure.

Conclusions: The study concludes that the combination of cadmium chloride and testosterone propionate results in a more aggressive tumor phenotype compared to either agent alone, suggesting a synergistic effect in prostate carcinogenesis. These findings underscore the importance of using combined hormonal and chemical induction models to better replicate human prostate cancer for experimental research. Further studies are recommended to explore molecular mechanisms and optimize induction protocols for improved translational relevance in prostate cancer research.

Histopathological Findings with Incidental Detection of Prostatic Carcinoma in TURP Specimen: A Retrospective Study in a Tertiary Care Hospital

Manoj Barman, Leena Talukdar, Jabin Musfique (Author) — Wed, 06 Aug 2025 06:40:28 +0000

Introduction: In adults prostate weighs upto 20 gms which is a pear shaped organ. Prostatic gland diseases leads to increase morbidity and moratlity in patients. Prostatic adenocarcinoma is one of the common malignancy among men in India. Transurethral resection of prostate (TURP) is one of the common procedures done by the urologist in cases of prostatomegaly.

Aims and Objective: This study was conducted to see various histopathological patterns of prostatic lesions in TURP specimens. Also to evaluate the incidence of incidental adenocarcinoma of prostste.

Materials and Methods: It was a retrospective study done for the duration of 1 year. Total 58 TURP cases were evaluated by retrieving their slides,blocks as well all the clinical informations. All the H & E slides were re examined and new slides were prepared from the paraffin blocks wherever required.

Results: In these study commonest lesion that we encountered in TURP specimen were benign prostatic hyperplasia (89.65%). BPH was associated with prostatitis in 20.69% of cases. Highest BPH cases were seen in the age group of 60-69 years. We also found one case of atypical adenomatoid hyperplasia (AAH) and one case of High grade PIN in our study. We detect 4 cases of incidental adenocarcioma in our study, incidence of which were 6.89 %. Most common age group of adenocarcinoma was 60-69 years. Out of 4 malignant cases 1 case showed perineural invasion in our study.

Conclusion: In TURP specimens, most common lesion are the benign prostatic hyperplasia. However TURP can detect incidental adenocarcinoma also. So it is very important to do routine histopathological examinations of all the TURP specimens to rule out malignancy.

The Therapeutic Potential of Curcuma longa (Turmeric) in the Management of Breast Cancer in Female Rats: Mechanisms and Molecular Targets

Maytham T. Qasim, Hayfaa A. Thijail, Lina A. Hameed, Zainab I. Mohammed (Author) — Wed, 06 Aug 2025 06:52:50 +0000

Background: Curcuma longa (turmeric), a traditional medicinal plant, has demonstrated significant antitumor properties in various cancer models. This study investigates the therapeutic efficacy of turmeric extract in the treatment of breast cancer in female rats, focusing on its mechanisms of action and molecular targets.

Methods: Female Wistar rats were induced with mammary tumors using 7,12-dimethylbenz [a] anthracene (DMBA). The treated group received standardized doses of turmeric extract orally for six weeks. Tumor volume, histopathological changes, apoptosis markers (e.g., caspase-3), and oxidative stress biomarkers (e.g., MDA, SOD) were evaluated.

Results: Rats treated with Curcuma longa showed a significant reduction in tumor size compared to the untreated group (p < 0.05). Histological analysis revealed increased apoptosis and reduced angiogenesis. Molecular assays indicated downregulation of NF-κB and upregulation of p53 expression.

Conclusion: Turmeric demonstrated potent antitumor effects in breast cancer–induced rats through modulation of oxidative stress, inflammation, and apoptosis pathways. These findings support further investigation into Curcuma longa as a complementary therapeutic agent in breast cancer management.

The Ratio of MicroRNA-21 to MicroRNA-195 as a Predictive and Prognostic Biomarker of Colorectal Carcinoma

Wed, 06 Aug 2025 07:04:44 +0000

Introduction: Colorectal carcinoma (CRC) is the fourth leading cause of cancer-related death worldwide and the third most common cancer in Indonesia. Due to its asymptomatic nature, CRC is often diagnosed at an advanced stage, making early detection critical. MicroRNAs (miRNAs), small non-coding single-stranded RNA molecules, have emerged as potential biomarkers for cancer.

Objective: This study aimed to determine the ratio profile of miR-21 and miR-195 as predictive and prognostic factors in colorectal carcinoma patients in Margono Soekarjo Hospital, Purwokerto, Indonesia.

Methods: This study was conducted with a cross-sectional study design on 31 colorectal carcinoma patients during the 2018-2020 period who still had remaining paraffin-embedded tissue blocks at the Anatomical Pathology Laboratory of Margono Soekarjo Hospital, Purwokerto, Indonesia. The expression levels of miR-21 and miR-195 were analyzed using quantitative polymerase chain reaction (qPCR). The Pearson correlation test assessed the association between miRNA expression and clinicopathological parameters.

Result: This study revealed that high miR-21 expression levels were significantly associated with poor prognosis in colorectal carcinoma patients, with p values of 0.027 and r = 0.398. Low miR-195 expression levels were significantly associated with poor colorectal carcinoma prognosis, with p values of 0.002 and r=0.533. A high miR-21/miR-195 expression levels ratio is significantly associated with the advanced colorectal carcinoma stage, with p values of 0.016 and r = 0.429.

Conclusion: A High ratio of miR-21/ miR-195 correlates with the advanced stage of colorectal carcinoma. The expression ratio of miR-21 to miR-195 may be a potential predictive and prognostic biomarker in colorectal carcinoma.

Exploring the Synergistic Anticancer Potential of Linagliptin and Esomeprazole in Cervical Cancer Cell Line: Mechanistic Insights into Targeting HSPB1, Hsp60

Wed, 06 Aug 2025 07:10:40 +0000

Objective: This study assessed the anticancer properties of the linagliptin-esomeprazole combination and investigated its molecular mechanism by analyzing its ability to target heat shock proteins.

Methods: Over 24 and 72 hours, a HeLa cell line was used to assess the cytotoxicity of linagliptin, esomeprazole, the linagliptin-esomeprazole mixture, and cisplatin. The safety and selective toxicity of the mixture were evaluated using the human-derived adipose tissue cell line NHF. The concentrations of linagliptin, esomeprazole, cisplatin, and the mixture ranged from 0.1 to 1000 µg/ml. The study involved an estimated combination index value to assess the potential synergistic effect of linagliptin and esomeprazole. The dose reduction index was used to evaluate decreases in the cytotoxic concentrations of the mixture components, indicating the mixture’s safety and potency. The study uses computational molecular docking simulations to evaluate the binding affinity of linagliptin and esomeprazole to different cancer-related heat shock proteins.

Results: Our study’s findings show that linagliptin, esomeprazole, and their combination inhibit the growth of cervical cancer cells, with the mixture being more cytotoxic than either individual drug and cisplatin. The interaction between linagliptin and esomeprazole demonstrated synergistic cytotoxicity, as the combination index score indicated. The mixture displayed selective toxicity toward cancer cells, suggesting a lower risk of adverse effects, supported by the selective toxicity and dose reduction indexes. The pilot study of computational molecular docking simulations involving various Heat shock proteins showed optimal interactions of linagliptin and esomeprazole with HSPB1 and Hsp60, respectively, with docking scores of -8.8 kcal/mol and -7.6 kcal/mol.

Conclusion: The findings from our study, including the MTT assay, combination index, dose reduction index, selective toxicity index, and computational docking simulations, indicate that the linagliptin–esomeprazole mixture is a promising, effective, safer, and cost-efficient alternative to traditional chemotherapy for cervical cancer.

Association of Estrogen Receptor TA Repeats with Endometrial and Ovarian Cancers in Basrah Province

Wed, 06 Aug 2025 07:23:03 +0000

Background: Ovarian and endometrial malignancies are complex diseases, since a defect in hormone balance can be the most important cause of tumor formation.

Aim of study: Examine and identify the association between ER TA repeats with endometrial and ovarian cancers in Basrah women.

Patients: Groups include 50 healthy controls and 50 cancer patients, divided into 20 endometrial cancer patients and 30 ovarian cancer patients.

Results and Discussion: The result shows TA 11–12 repeats are the most common in endometrial cancer in 68% of cancer patients, followed by TA≥10 in 8% and 4% for both 13–14 repeats and ≤15, whereas TA repeats 11–12 and ≤15 repeats are the most common in ovarian cancer in 22% for each one, followed by ≥10 TA in 10% and 13–14 in 6%. The control groups have four groups of repeat numbers: 11–12 TA repeat in 68%, 13–14 in 20%, ≤15in 10%, and ≥10 in 2%. Simultaneously, a substantial association exists between the two types of cancers and the TA repeat length variation of the estrogen receptor type alpha.

Conclusion: The length of the TA repeat in estrogen receptor alpha has a significant risk for ovarian and endometrial cancer.

VEGF as a Predictor of Mitotic Activity and Brain Invasion in Meningioma

Sat, 23 Aug 2025 09:40:48 +0000

Background: Meningiomas exhibit variable biological behavior, with mitotic activity and brain invasion being critical histopathological markers of aggressiveness. While Vascular Endothelial Growth Factor (VEGF) is implicated in tumor progression, its precise role in driving these specific aggressive features in meningioma remains to be fully elucidated. This study investigated the association between immunohistochemical VEGF expression, mitotic activity, and brain invasion in meningioma.

Methods: We conducted a retrospective, cross-sectional analysis of 73 surgically resected meningioma specimens. VEGF expression was semi-quantitatively scored via immunohistochemistry (negative, weak, moderate, strong) and correlated with mitotic counts (per 10 high-power fields, HPF) and the presence of brain invasion. Associations were assessed using the chi-square test.

Results: High VEGF expression was significantly associated with a higher mitotic index (≥4 mitoses/10 HPF) (p=0.005); notably, 80% (8/10) of cases with high mitotic activity demonstrated moderate to strong VEGF expression. Furthermore, VEGF expression was significantly elevated in brain-invasive meningiomas compared to their non-invasive counterparts (p=0.007), with 75% (3/4) of invasive cases exhibiting strong VEGF expression.

Conclusion: Elevated VEGF expression strongly and statistically significantly correlates with both increased mitotic activity and brain invasion in meningiomas. These findings underscore VEGF’s crucial role as a mediator of tumor proliferation and parenchymal infiltration, positioning it as a potential biomarker for aggressive meningioma and a promising target for future therapeutic interventions.

Capacity of Thymidylate Synthase and Dihydropyrimidine Dehydrogenase mRNA Expression to Predict Neoadjuvant Chemotherapy Response of 5fu Regimen in Advanced Colorectal Cancer: A Cross-Sectional Study

Sat, 23 Aug 2025 09:49:23 +0000

Background: Chemotherapy is an important component of colorectal cancer treatment. Despite its success in inducing tumor cell death, chemotherapy has been constrained by resistance and adverse side effects. Therefore, predictive markers are required to ensure that the appropriate chemotherapy is administered based on the individual patient. This study aimed to correlate the mRNA expression of the TS and DPD genes with the tumor and CEA responses to the 5FU chemotherapy regimen.

Methods: This was a cross-sectional study with a prognostic test design. Measurements of tumor mass and tissue sampling were done prior to chemotherapy. CT scans were performed to measure tumor size pre-chemotherapy and after two cycles of treatment with a lag time of three weeks. The mRNA expression of the TS and DPD genes was then evaluated in each group.

Results: The mean value of the mRNA expression of the TS gene (9.555±1.693) showed an insignificant correlation with clinical response p=0.195 (p<0.05). However, the mean value of the mRNA expression of the DPD gene (7.461±1.088) was significantly correlated with clinical response p=0.003 (p<0.05).

Conclusion: DPD mRNA can be considered a marker of chemotherapy responsiveness when choosing a chemotherapy regimen.

Paclitaxel-Loaded PBCA Nanoparticles for Targeted Drug Delivery in Ovarian Cancer

Sat, 23 Aug 2025 11:19:09 +0000

Overview: Resistance to paclitaxel remains a critical barrier in the effective treatment of ovarian cancer, often resulting in reduced clinical responses and increased recurrence rates. Nanoparticle-mediated drug delivery has emerged as a promising strategy to overcome such resistance by enhancing drug bioavailability and targeting tumor cells more precisely. The present study focuses on the formulation of poly(butyl cyanoacrylate) (PBCA) nanoparticles to facilitate controlled paclitaxel delivery and improve its therapeutic efficacy against drug-resistant ovarian cancer cells.

Methods: Paclitaxel-loaded PBCA nanoparticles were synthesized using a mini-emulsion polymerization technique. Physicochemical properties were assessed by measuring hydrodynamic size, polydispersity index (PDI), zeta potential, and in vitro drug release behavior. Morphological evaluation was conducted via Scanning Electron Microscopy (SEM) to confirm particle uniformity and surface characteristics. Cytotoxicity was examined against the A2780CIS ovarian cancer cell line following 48 hours of exposure to the nanoformulation and free paclitaxel.

Results: The formulated nanoparticles displayed a spherical morphology with an average diameter of 355 nm, a PDI of 0.29, and a surface charge of –18.4 mV. Drug release profiling demonstrated a sustained and controlled release, with approximately 42% of paclitaxel released over 40 hours under physiological conditions. Cellular viability assays revealed that treatment with paclitaxel-loaded PBCA nanoparticles led to a 68% reduction in cell viability, significantly outperforming free paclitaxel, which showed a 41% decrease under identical conditions (p < 0.01).

Conclusion: PBCA nanoparticles exhibited favorable physicochemical characteristics and enhanced anticancer activity in paclitaxel-resistant ovarian cancer cells. These findings support their potential application as a targeted and efficient nanocarrier system for improving the therapeutic index of chemotherapeutic agents in drug-refractory malignancies.

Toward Precision Oncology in Ovarian Cancer: Dual PD-L1 and CD44 Biomarker Profiling for Recurrence Risk Assessment

Sat, 23 Aug 2025 11:52:53 +0000

Background: Epithelial ovarian carcinoma (EOC) remains one of the most fatal gynecologic cancers, often presenting at an advanced stage and prone to frequent recurrence despite aggressive treatment. Identifying reliable prognostic biomarkers is essential for improving patient stratification and optimizing adjuvant treatment strategies. This study investigated the expression patterns of programmed death-ligand 1 (PD-L1) and CD44, a recognized cancer stem cell (CSC) marker, and examined their relationships with clinicopathological features, recurrence risk, and survival outcomes in EOC.

Methods: A retrospective study was performed involving 90 patients with histologically confirmed EOC managed at National Cancer Institute, Cairo University. Immunohistochemistry was utilized to assess PD-L1 and CD44 expression in tumor samples. The associations between biomarker expression, clinical and pathological variables, recurrence-free survival (RFS), and overall survival (OS) were analyzed using Kaplan–Meier survival curves, multivariate logistic regression, and Cox proportional hazards models.

Results: PD-L1 was expressed in 42.2% of tumors and showed significant associations with advanced International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.017), higher tumor grade (p=0.004), presence of distant metastasis (p=0.002), and increased recurrence rates (p<0.001). CD44 positivity was identified in 71.1% of cases, predominantly among serous carcinoma subtypes (p=0.010), and was likewise linked to a higher recurrence risk (p<0.001). Patients with PD-L1-positive tumors exhibited a notably shorter median RFS compared to PD-L1-negative patients (31.3 vs. 54.7 months, p<0.001), as did CD44-positive individuals relative to their CD44-negative counterparts (36.3 vs. 56.7 months, p<0.001). Neither biomarker, however, demonstrated a statistically significant effect on OS during a median follow-up of approximately five years. Notably, patients with concurrent PD-L1 and CD44 expression experienced the poorest RFS outcomes (mean 30.9 months), while those negative for both markers showed the most favorable prognosis (mean 56.6 months, p<0.001). Multivariate analysis confirmed PD-L1 (OR 4.86, p=0.003) and CD44 (OR 9.61, p=0.006) as independent predictors of recurrence.

Conclusions: The expression of PD-L1 and CD44 in EOC is independently associated with an elevated risk of disease recurrence, and their co-expression identifies a particularly high-risk patient subset. Although neither marker significantly influenced overall survival within the study’s follow-up period, their combined assessment holds promise for enhancing prognostic models and guiding the selection of patients for intensified monitoring and clinical trials exploring immune checkpoint blockade and CSC-targeted therapies.

Advances in Uveal Melanoma: From Molecular Pathogenesis to Precision Diagnostics and Personalized Therapies: Narrative Overview

Mon, 14 Jul 2025 05:01:37 +0000

Objective: This review aims to summarize recent progress in the molecular understanding, diagnostic strategies, and treatment innovations in uveal melanoma (UM), the most common primary intraocular malignancy in adults. Emphasis is placed on the integration of precision diagnostics and emerging therapies that may improve clinical outcomes in high-risk cases.

Materials and Methods: A narrative literature review was conducted using databases including PubMed, Scopus, Web of Science, and Google Scholar, covering the years 2020 to 2024. Keywords used included “uveal melanoma,” “liquid biopsy,” “circulating tumor cells,” “gene mutations,” “immunotherapy,” and “precision oncology.” Relevant peer-reviewed articles, clinical trials, and reviews were selected based on methodological quality and relevance to the scope of the review.

Results: Uveal melanoma most frequently arises in the choroid and is genetically distinct from cutaneous melanoma. It is primarily driven by mutations in guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), guanine nucleotide-binding protein G(q) subunit alpha-11 (GNA11), BRCA1 associated protein-1 (BAP1), eukaryotic translation initiation factor 1A X-linked (EIF1AX), and splicing factor 3B subunit 1 (SF3B1). These mutations activate key signaling pathways such as mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), influencing prognosis and therapeutic response. Diagnostic advancements include high-resolution imaging and liquid biopsy techniques, which enable detection of circulating tumor cells, circulating tumor DNA, and microRNAs. Standard treatments include radiation therapy (plaque brachytherapy) and surgical interventions. Novel therapeutic approaches such as tebentafusp (a T-cell receptor therapy), oncolytic viruses, chimeric antigen receptor (CAR) T-cell therapy, suicide gene constructs, and RNA interference show promise in clinical and preclinical settings.

Conclusion: A precision medicine approach that integrates molecular diagnostics, artificial intelligence-enhanced liquid biopsy, and novel systemic therapies is transforming the management of uveal melanoma. These innovations may enable earlier detection, more accurate risk stratification, and targeted treatment, potentially improving survival and preserving vision in affected patients.