Tag: nevin manimala

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2529-2537. doi: 10.31557/APJCP.2024.25.7.2529.

ABSTRACT

BACKGROUND: Despite advances in breast carcinoma therapies, drug resistance mechanisms as anti-apoptosis and anti-pyroptosis limit the application of these therapies. This work assesses the immunohistochemical (IHC) expression of Caspase1 and EGFR in breast carcinoma and analyzes their clinicopathological associations as prognostic markers and potential therapeutic targets. Caspase1/EGFR expression patterns are utilized to specify breast carcinoma patients who may benefit from these therapies.

METHODS: After reviewing the hematoxylin and eosin-stained slides and the routine breast carcinoma IHC stains (estrogen receptors, progesterone receptors, HER2/NEU, Ki-67) by two pathologists and preparation of tissue microarray blocks, anti-Caspase-1 and EGFR IHC staining was performed using Horseradish Peroxidase (HRP) technique. Intensity and percentage-based scoring was applied dividing the 153 included breast carcinomas into Caspase1-negative and positive expression groups; and EGFR low and overexpression groups. Groups were statistically analyzed in relation to age, tumor size, histological and molecular subtype, grade, nodal status, metastasis/recurrence, TNM stage and Ki-67 proliferation index. Kaplan-Meier’s analysis was used to compare disease-free survival (DFS) and overall survival (OS). Combined patterns based on Caspase1 and EGFR expression status were created to stratify patients into prognostic groups.

RESULTS: Caspase1 was positive in 54.2% of breast carcinomas and its positivity was significantly associated with smaller tumor size, absence of metastasis/recurrence, luminal A and B molecular subtypes and longer OS (p<0.05). EGFR overexpression was detected in 32.7% of carcinomas and was significantly associated with larger tumor size, TNBLBC and a shorter OS (p<0.05). Caspase1-negative/EGFR-overexpression pattern comprised 14.4% of carcinomas and had the worst prognostic associations including larger tumor size, metastasis/recurrence, TNBLBC subtype and shortest OS (p=0.002, 0.002, 0.004 and ≤0.001 respectively). Conclusions: Combined Caspase1/EGFR IHC expression may provide a tool for selection of patients who benefit from combined EGFR-inhibitors with miR-155-5p down-regulators or photodynamic therapy via induction of apoptosis/pyroptosis in EGFR-overexpression carcinomas through enhanced Caspase1 signaling.

PMID:39068588 | DOI:10.31557/APJCP.2024.25.7.2529

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2515-2527. doi: 10.31557/APJCP.2024.25.7.2515.

ABSTRACT

BACKGROUND: Cluster of differentiation 47 (CD47) has been identified as a new immune checkpoint. The exact role of CD47 in prognosis of breast cancer remains unclear. This study aims to evaluate immunohistochemical (IHC) expression of CD47 in breast cancer, and to measure the density of tumor associated macrophages (TAMs) infiltration by CD68 IHC staining. Furthermore, assessing the relations of CD47 and CD68 expression to different clinicopathological variables and evaluating the prognostic role of CD47 and CD68 in breast cancer cases.

METHODS: This retrospective cohort study included 200 diagnosed primary breast cancer cases who underwent surgical resection at the Oncology Center of Mansoura University (OCMU), Faculty of Medicine, Egypt. Clinicopathological and survival data were collected. IHC for CD47 and CD68 was performed.

RESULTS: Among 200 breast cancer cases, high CD47 expression was detected in 89 cases (44.5%). CD47 high expression was significantly associated with presence of distant metastasis (P=0.04), advanced TNM stage (P=0.02), ER & PR negativity (P=0.04 & 0.004 respectively), and molecular subtype (P=0.03). Their was a statistically significant association between CD47 and CD68 expression (P=0.002). CD47 high expression was found to predict poor overall survival, but it is not considered alone as independent poor prognostic factor by multivariate analysis. Multivariate analysis spotted combined high expression of CD47 and CD68 as an independent prognostic predictor for shorter OS in breast cancer patients (P=0.002).

CONCLUSION: CD47 high expression is related to poor prognosis in breast cancer patients especially when associated with high CD68+TAMs infiltration. Therefore, CD47 is a promising prognostic and therapeutic target in breast carcinoma that may direct selection of patients for immunotherapy.

PMID:39068587 | DOI:10.31557/APJCP.2024.25.7.2515

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2499-2507. doi: 10.31557/APJCP.2024.25.7.2499.

ABSTRACT

OBJECTIVE: High grade glioma (HGG) is considered a lethal disease with a high recurrence rate. There is no standard of care in recurrent HGG. Many treatment options are present, such as resurgery, systemic therapy, and re-irradiation. Re-irradiation seems to be a promising option. In this study, we aimed at comparing the efficacy and toxicity of two re-irradiation protocols.

METHODS: Forty patients with recurrent HGG were randomized equally into two arms. Arm A received 30 Gy/10f/2w, and arm B received stereotactic body radiotherapy (SBRT) 30 Gy/5f/1w. Concurrent temozolamide (TMZ) was given in both arms. Median progression free survival (PFS) and overall survival (OS) were calculated, and brain MRI was done after 2 months of radiotherapy and then every 2 months, with documented toxicity using the Common Terminology of Adverse Events version 5 (CTCAE).

RESULTS: The median follow-up time after the re-irradiation course was 11 months (range 8-15 months). The median PFS after recurrence was 6.4 months (95% CI 5.3-7.4), the median OS after recurrence was 8.6 months (95% CI 7.5-8.7), and the median total OS form date of diagnosis was 18.5 months (95% CI 17.3-19.8) among the included patients. There was a statistically significant difference in PFS favoring arm B, with a median PFS of 7.3 versus 6.2 months in arm A, with p values of 0.004. There was no statistically significant difference in in median OS (9.3 months in arm B versus 8.4 months in arm A) with p values of 0.088. All patients tolerated their treatment well, and acute and subacute G1-G2 toxicity, consisting of headache, malaise, and nausea, were recorded during and shortly after the end of the re-irradiation course.

CONCLUSION: Re-irradiation in recurrent HGG by both protocols is safe and effective, with a significant improvement in PFS in SBRT arm but no significant improvement in OS.

PMID:39068585 | DOI:10.31557/APJCP.2024.25.7.2499

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2483-2492. doi: 10.31557/APJCP.2024.25.7.2483.

ABSTRACT

BACKGROUND: Pancreatic cancer is a devastating disease with a poor prognosis, causing significant physical and psychological distress that detrimentally impacts patients’ quality of life.

AIM: This study aimed to comprehensively assess the physical and psychological status of newly diagnosed pancreatic cancer patients.

METHODS: A cohort of 138 newly diagnosed patients completed standardized assessments, including the Edmonton Symptom Assessment System (ESAS), Patient Health Questionnaire-9 (PHQ-9), Mini-Mental State Examination (MMSE), and Distress Thermometer (DT). Data were analysed using descriptive statistics.

RESULTS: The ESAS scores revealed high symptom burden, with mean scores of 6.8 for pain, 7.2 for fatigue, and 4.9 for depression. Measures of well-being indicated low scores, with means of 2.3 for physical well-being, 1.5 for social/family well-being, and 1.7 for emotional well-being. Distress levels were also high, with a mean score of 7.6 on the DT.

CONCLUSION: Newly diagnosed pancreatic cancer patients experience substantial physical and psychological challenges, including severe symptom burden, distress, depressive symptoms, and cognitive impairment. Holistic care approaches that prioritize symptom management and address psychological distress are essential to improve patient outcomes and enhance overall well-being.

PMID:39068583 | DOI:10.31557/APJCP.2024.25.7.2483

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2467-2474. doi: 10.31557/APJCP.2024.25.7.2467.

ABSTRACT

AIM: This study aimed to evaluate the efficacy of static or step-and-shoot intensity-modulated radiotherapy (ssIMRT) and dynamic intensity-modulated radiotherapy (dIMRT) delivery techniques for various treatment sites.

MATERIALS AND METHODS: The treatment planning system (TPS) was utilized to develop optimal treatment plans for twenty-seven patients selected for this comparative study, including nine with head and neck cancer, nine with prostate cancer, and nine with cervical cancer. The prescribed doses were 7000cGy/33fr, 7425cGy/33fr, and 5000cGy/25fr for the nasopharynx, prostate, and cervix cases, respectively, in both ssIMRT and dIMRT delivery techniques. Plans were generated using the Monaco treatment planning system with a 6MV photon beam and nine equidistant fields. Plan evaluation criteria included dose-volume histogram analysis, dose homogeneity index, conformity index, radiation delivery time, and monitor unit requirements.

RESULTS: All plans were optimized to ensure that 98% of the planning target volume (PTV) received at least 95% of the prescribed dose, while meeting the planning objectives for organs at risk. dIMRT plans exhibited superior conformity (CI = 0.85 ± 0.05) compared to ssIMRT plans (CI = 0.79 ± 0.08), with statistically significant differences (P < 0.01). Inhomogeneity within the PTV was significantly higher in ssIMRT plans (HI = 0.10 ± 0.02) compared to dIMRT plans (HI = 0.09 ± 0.01), with a significant difference (P < 0.01). Delivery time per fraction was significantly lower in dIMRT compared to ssIMRT (P < 0.01). Furthermore, dIMRT plans required a higher mean monitor unit value (1335.4 ± 172.2) compared to ssIMRT plans (974.4 ± 133.6) with a significant difference (P < 0.001).

CONCLUSION: The findings of this study indicate that dIMRT provides improved target coverage, homogeneity, and conformity while reducing treatment delivery time compared to ssIMRT.

PMID:39068581 | DOI:10.31557/APJCP.2024.25.7.2467

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2457-2466. doi: 10.31557/APJCP.2024.25.7.2457.

ABSTRACT

BACKGROUND: Total neoadjuvant therapy (TNT) before surgical intervention represents a unique therapeutic approach for the management of locally advanced rectal cancer (LARC) and has witnessed a notable rise in utilization within recent years. However, the efficacy and safety of this treatment remain subjects of ongoing debate and investigation. This randomized controlled trial aimed to evaluate the potential impact of administering induction chemotherapy (IC) before the conventional neoadjuvant concomitant chemoradiotherapy (nCRT) in LARC patients.

MATERIALS & METHODS: patients with resectable stage II-III LARC were randomly allocated to receive either biweekly 6 cycles of FOLFOX4 regimen as IC followed by CRT and total mesorectal excision (TME) (experimental group) or nCRT followed by TME (control group). The primary endpoint was the rate of pathological complete response (pCR). The secondary endpoints encompassed the evaluation of treatment-related adverse events as well as the assessment of survival outcomes.

RESULTS: 67 patients were enrolled in this study (32 in the experimental group and 35 in the control group). The median age of the patients was 45 years. Stage IIIB was observed in 46.3% of the patients. The patients who underwent induction chemotherapy demonstrated a notably higher rate of achieving pCR in comparison to the control group (28.1% vs 8.6%; P=0.001). There were no statistically significant differences observed in terms of their toxicity profile and survival outcomes.

CONCLUSIONS: Implementation of induction chemotherapy utilizing the FOLFOX4 regimen has demonstrated a notable enhancement in the rate of pathological complete response. However, this improvement does not appear to translate into significant advancements in overall survival outcomes.

PMID:39068580 | DOI:10.31557/APJCP.2024.25.7.2457

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2415-2420. doi: 10.31557/APJCP.2024.25.7.2415.

ABSTRACT

BACKGROUND: MiR-34b/c takes an important role in various aspects of carcinogenesis. Notably, pri miR34b/c (rs4938723) T>C polymorphism has been identified as a significant biomarker in various kinds of cancer. The objective of this study was to explore whether pri-miR34b/c rs4938723) T>C was associated with breast cancer susceptibility. Moreover, the association of pri-miR34b/c (rs4938723) T>C and clinicopathologic data, including survival outcomes, were studied in Thai breast cancer patients.

METHODS: DNA extracted from the blood of 100 Thai female breast cancer patients and 100 Thai healthy women were investigated for pri-miR34b/c (rs4938723) T>C polymorphism using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP).

RESULTS: There was no statistically significant difference between the frequency of pri miR34b/c (rs4938723) T>C genotype between Thai breast cancer patients and normal subjects. This study showed that there is no association between pri-miR34b/c (rs4938723) genotypes and breast cancer susceptibility, clinicopathologic parameters, and survival time. However, age greater than 50 and histologic grade III were the prognostic factors affecting survival in breast cancer patients (p=0.017, p=0.010, respectively).

CONCLUSION: The pri-miR34b/c (rs4938723) genotypes had no association with cancer susceptibility and clinicopathologic parameters in Thai breast cancer patients. Patients with older age and patients with higher histologic grade, but not the pri miR34b/c (rs4938723) genotype, affected survival time among breast cancer patients.

PMID:39068575 | DOI:10.31557/APJCP.2024.25.7.2415

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2361-2369. doi: 10.31557/APJCP.2024.25.7.2361.

ABSTRACT

BACKGROUND: Accurate estimation of body composition, particularly, Body Cell Mass (BCM), which is independent of hydration status is important in children with cancer. This study aimed to accurately measure the anthropometry and body composition of children with Acute Lymphoblastic Leukaemia (ALL) at diagnosis and compare them with healthy children from South India.

METHODS: This was a cross-sectional study in children aged 2 to 8 y with ALL from St. John’s Medical College Hospital, Bengaluru, and age and sex-matched, normal-weight children recruited as controls from communities. Anthropometry (weight, height, circumferences), skinfolds and body composition measurements using a whole-body potassium counter were performed. Body mass index-for-age, weight and height for age z-scores were calculated using WHO child growth standards. Biochemical markers, dietary intake and physical activity details were recorded. Categorical and continuous variables were analyzed by chi-square and independent t-tests respectively. Results: The mean age of the children with ALL (n = 39) was 4.6±1.9 y and control group (n=39) was 4.7±1.9 y; 61.5% were boys. The prevalence of underweight, overweight/obesity and stunting were 17.9%, 7.7%, and 10.3% respectively. The mean weight and height, of children with ALL and children in the control group were 16.8±6.2 kg and 16.4±4.1 kg, 104.3±14.9 cm and 105.1±12.2 cm, respectively with no statistical difference. Children with ALL showed lower body cell mass index kg/m2 (4.6± 0.8), compared to children in the control group (4.7±0.9) p=0.527, but higher fat mass index kg/m2 (3.6±1.1 vs. 3.4±0.8) p=0.276.

CONCLUSION: At diagnosis, anthropometric and body composition measurements were similar between children with ALL and children in the control group. The BCM showed a non-significant trend of being lower in children with ALL, which requires close monitoring during treatment. Evaluating early-stage nutritional status and body composition can help in planning appropriate interventions during treatment to prevent long term non-communicable diseases.

PMID:39068569 | DOI:10.31557/APJCP.2024.25.7.2361

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2319-2327. doi: 10.31557/APJCP.2024.25.7.2319.

ABSTRACT

BACKGROUND: Prostate cancer is the most common tumor in men worldwide with a poor prognosis. In recent years, studies have revealed that pyroptosis can affect the tumor immune microenvironment. However, the relationship between the immune microenvironment regulated by pyroptosis-related genes and the prognosis of prostate cancer is still unclear.

METHODS: Thirty-three cell death-associated genes were selected from a literature review. The “DESeq2” R package was used to identify differentially expressed cell death-associated genes between normal prostate tissue (GTEx) and prostate cancer tissue (TCGA) samples. Biological functional enrichment analysis of differentially expressed cell death genes was performed using R statistical software packages, such as “clusterProfiler,” “org.Hs.eg.db,” “enrichplot,” “ggplot2,” and “GOplot.” Univariate Cox and LASSO Cox regression analyses were conducted to identify prognostic genes associated with the immune microenvironment using the “survival” package. Finally, a predictive model was established based on Gleason score, T stage, and cell death-associated genes.odel was established based on Gleason score, T stage, and cell death-associated genes.

RESULTS: Seventeen differentially expressed genes related to pyroptosis were screened out. Based on these differentially expressed genes, biological function enrichment analysis showed that they were related to pyroptosis of prostate cells. Based on univariate Cox and (LASSO) Cox regression analysis, four pyroptosis-related genes (CASP3, PLCG1, GSDMB, GPX4) were determined to be related to the prognosis of prostate cancer, and the immune correlation analysis of the four pyroptosis-related genes was performed. The expression of CASP3, PLCG1 and GSDMB was positively correlated with the proportion of immune cells, and the expression of GPX4 was negatively correlated with the proportion of immune cells. A predictive nomogram was established by combining Gleason score, T and pyroptosis genes. The nomogram was accompanied by a calibration curve and used to predict 1 -, 2 -, and 5-year survival in PAAD patients.

CONCLUSION: Cell death-associated genes (CASP3, PLCG1, GSDMB, GPX4) play crucial roles in modulating the immune microenvironment and can be used to predict the prognosis of prostate cancer.

PMID:39068564 | DOI:10.31557/APJCP.2024.25.7.2319

Asian Pac J Cancer Prev. 2024 Jul 1;25(7):2311-2317. doi: 10.31557/APJCP.2024.25.7.2311.

ABSTRACT

OBJECTIVES: Investigation of diagnostic and prognostic relevance of BRCA1 immunohistochemistry (IHC) in endometrial carcinoma.

METHODS: Ninty four specimens of endometrial carcinomas were evaluated. Full sections stained with hematoxylin & eosin were revaluated for assessment of tumor type, grade, myometrial, & lympho-vascular invasion (LVI). Tissue microarray blocks were constructed using the pencil tip method and immunostained with Anti-BRCA1 antibody. BRCA1 was correlated with clinicopathological parameters as well as disease free survival and overall survival.

RESULTS: There was a statistically significant difference (P=0.001) between serous and endometroid carcinomas regarding BRCA1 expression where most cases of serous carcinoma showed negative expression. No statistically significant difference was found between BRCA1 positive and negative cases regarding disease free survival (DFS) or overall survival. Serous histotype, high grade, advanced stage, and omental deposits were the parameters significantly associated with decreased DFS.

CONCLUSION: Results of this study can support inclusion of BRCA1 IHC in a panel to differentiate both endometroid and serous carcinomas. The current study found no prognostic relevance for BRCA1 in terms of overall survival and disease-free survival.

PMID:39068563 | DOI:10.31557/APJCP.2024.25.7.2311