4-Acetylantroquinonol B induced DNA damage response signaling and apoptosis via suppressing CDK2/CDK4 expression in triple negative breast cancer cells.

BACKGROUND: Triple-negative breast cancer (TNBC) has a more aggressive phenotype and poorer prognosis than hormone receptor (HR+) and human epidermal growth factor receptor (HER2 -) subtypes. Inhibition of cyclin-dependent kinase (CDK)4 and CDK6 was successful in patients with advanced metastatic HR+/HER2- breast cancer, but those with TNBC exhibited low or no response to this therapeutic approach. This study investigated the dual therapeutic targeting of CDK2 and CDK4 by using 4-acetyl-antroquinonol B (4-AAQB) against TNBC cells. METHODS: We examined the effects of CDK2, CDK4, and CDK6 inhibition through 4-AAQB treatment on TNBC cell lines and established an orthotropic xenograft mouse model to confirm the in vitro results of inhibiting CDK2, CDK4, and CDK6 by 4-AAQB treatment. RESULTS: High expression and alteration of CDK2 and CDK4 but not CDK6 significantly correlated with poor overall survival of patients with breast cancer. CDK2 and CDK4 were positively correlated with damage in DNA replication and repair pathways. Docking results indicated that 4-AAQB was bound to CDK2 and CDK4 with high affinity. Treatment of TNBC cells with 4-AAQB suppressed the expression of CDK2 and CDK4 in vitro. Additionally, 4-AAQB induced cell cycle arrest, DNA damage, and apoptosis in TNBC cells. In vivo study results confirmed that the anticancer activity of 4-AAQB suppressed tumor growth through the inhibition of CDK2 and CDK4. CONCLUSION: The expression level of CDK2 and CDK4 and DNA damage response (DDR) signaling are prominent in TNBC cell cycle regulation. Thus, 4-AAQB is a potential agent for targeting CDK2/4 and DDR in TNBC cells.

ESR1 PvuII polymorphism: from risk factor to prognostic and predictive factor of the success of primary systemic therapy in advanced breast cancer.

BACKGROUND: The ESR1 gene encodes Estrogen Receptor alpha (ERα), which plays a role in the tumourigenesis of breast cancer. A single nucleotide polymorphism (SNP) in intron 1 of this gene called ESR1 PvuII (rs2234693) has been reported to increase the risk of breast cancer. This study aimed to investigate the ESR1 PvuII polymorphism as a prognostic and predictive factor guiding the choice of therapy for advanced breast cancer. METHODS: This retrospective study was conducted in 104 advanced breast cancer patients at Dharmais Cancer Hospital from 2011 to 2018. The ESR1 PvuII polymorphism was analysed by Sanger sequencing of DNA from primary breast tumour samples. RESULTS: The percentages of patients with ESR1 PvuII genotypes TT, TC, and CC were 42.3, 39.4, and 18.3%, respectively. Looking at prognosis, patients with ESR1 PvuII TC + CC had shorter overall survival than those with the TT genotype [HR = 1.79; 95% CI 1.05-3.04; p = 0.032]. As a predictive marker, TC + CC was associated with shorter survival (p = 0.041), but TC + CC patients on primary hormonal therapy had a median overall survival longer than TC + CC patients on primary chemotherapy (1072 vs 599 days). CONCLUSION: The ESR1 PvuII TC + CC genotypes confer poor prognosis in advanced breast cancer, but these genotypes could be regarded as a good predictor of the therapeutic effect of hormonal treatment.

Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors.

BACKGROUND: Obesity and other metabolic comorbidities affect over 10% of patients with breast cancer and are closely related with adverse outcomes. Although metabolic comorbidities among breast cancer patients in low- and middle-income countries are suggested to be lower, only a few studies are currently available. Effective management of metabolic comorbidities in cancer patients has been associated with better outcomes. METHODS: Non-metastatic breast cancer patients (N = 1081) treated in our department (2014-2018) were monitored for the presence of high Body Mass Index (BMI), diabetes or glucose intolerance, dyslipidemia, and hypertension and the development of recurrent metastatic diseases during a median follow-up of 3.9 years. RESULTS: Glucose intolerance, hypertension, dyslipidemia, and BMI ≥ 27.7 kg/m2 considered at risk for metabolic comorbidities were found in 26.5, 42.6, 27.7, and 23.3% of breast cancer patients, respectively. Diabetes or glucose intolerance and having both glucose intolerance and dyslipidemia were associated with the risk of recurrent metastatic disease (OR = 1.442, 95%CI = 1.071-1.943, p = 0.016 and OR = 1.495, 95%CI = 1.090-2.049, p = 0.010; respectively). Having three or more metabolic comorbidities was significantly associated with the risk of recurrent metastatic disease (OR = 1.647, 95%CI = 1.139-2.382, p = 0.008) compared to patients without any comorbidity. The metabolic comorbidities were distributed unevenly among breast cancer subtypes. A significant association with recurrent metastatic disease was found in the Luminal B-like subtype. In post-menopausal patients, having more than three comorbidities was associated with a higher risk of recurrent metastatic disease compared to those without any comorbidity (OR = 2.000, 95%CI = 1.035-3.067, p = 0.001). The risks of having three or more metabolic comorbidities were significantly higher in breast cancer survivors who were obese, lived in an urban area, and received hormonal therapy of aromatase inhibitors. CONCLUSION: Metabolic comorbidities were frequently found in breast cancer patients and were associated with higher risks to develop recurrent metastatic disease, particularly in post-menopausal women. Subsequent larger studies are needed to better understand the association of metabolic comorbidities with patients' quality of life and prognosis, and to explore the potential combination of clinical intervention and lifestyle modification in breast cancer survivors to treat as well as reduce their impact.

Risk factors of distant metastasis after surgery among different breast cancer subtypes: a hospital-based study in Indonesia.

BACKGROUND: More than one third of breast cancer patients including those that are diagnosed in early stages will develop distant metastasis. Patterns of distant metastasis and the associated risks according to the molecular subtypes are not completely revealed particularly in populations of patients with delayed diagnosis and advanced stages. METHODS: Breast cancer patients (n = 1304) admitted to our institute (2014-2017) were evaluated to identify the metastatic patterns and the associated risks. Metastatic breast cancers at diagnosis were found in 245 patients (18.7%), and 1059 patients were then grouped into non-metastatic and metastatic groups after a median follow-up of 3.8 years. RESULTS: Infiltration of the tumor to the skin and chest wall prevailed as the most powerful predictor for distant metastasis (OR 2.115, 95% CI 1.544-2.898) particularly in the luminal A-like subtype (OR 2.685, 95% CI 1.649-4.371). Nodal involvement was also significantly associated with the risk of distant metastasis (OR 1.855, 95% CI 1.319-2.611), and the risk was higher in the Luminal A-like subtype (OR 2.572, 95% CI 1.547-4.278). Luminal A-like subtype had a significant higher risk of bone metastasis (OR 1.601, 95% CI 1.106-2.358). In respect to treatment, a combination of anthracyclines and taxanes-based chemotherapy was significantly associated with lower distant organ spread in comparison with anthracycline-based chemotherapy (OR 0.510, 95% CI 0.355-0.766) and the effect was stronger in Luminal A-like subtype (OR 0.417, 95% CI 0.226-0.769). Classification into Luminal and non-Luminal subtypes revealed significant higher risks of bone metastasis in the Luminal subtype (OR 1.793, 95% CI 1.209-2.660) and pulmonary metastasis in non-Luminal breast cancer (OR 1.445, 95% CI 1.003-2.083). CONCLUSION: In addition to guiding the treatment plan, a comprehensive analysis of clinicopathological variables including the molecular subtypes could assist in the determination of distant metastasis risks of breast cancer patients. Our study offers new perspectives concerning the risks of distant metastasis in breast cancer subtypes in order to plan intensive surveillance or escalation of treatment particularly in a setting where patients are predominantly diagnosed in late stages.

Expression of Circulating MicroRNA-141 in Epithelial Ovarian Cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is a lethal disease due to late diagnosis and lack of effective screening methods. MicroRNA (miR/miRNA) plays an important role in ovarian carcinogenesis and may serve as a non-invasive biomarker for EOC. This study aimed to assess miR-141 expression in the blood plasma of patients with EOC and healthy subjects and determine its association with the clinical stage of EOC. METHODS: This cross-sectional study used blood plasma from 30 newly diagnosed untreated patients with EOC and 25 healthy subjects. The mean age was 47.73 (SD = 10.29) years for EOC and 44.48 (SD = 16.14) years for healthy subject. The total RNA was isolated from blood plasma and reversed transcribed to obtain cDNA. The expression of miR-141 was measured by real-time quantitative polymerase chain reaction (qRT-PCR), and calculated using 2-ΔΔCt methods. The data were analysed using Mann-Whitney test. RESULTS: The expression of miR-141 was upregulated 8.41 fold in the blood plasma of EOC patients compared to healthy controls (P < 0.001). Expression of miR-141 in the advanced stage was upregulated 4.2 fold compared to the early stage (P < 0.001). CONCLUSION: The miR-141 was upregulated in the blood plasma of EOC and associated with an advanced stage of disease, suggesting it has potential as a biomarker for EOC detection.

Pathological profiles and clinical management challenges of breast cancer emerging in young women in Indonesia: a hospital-based study.

BACKGROUND: Breast cancer diagnosed at a young age is often associated with aggressive biology, advanced stage, and unfavorable prognosis. The median age of breast cancer diagnosis in Indonesia is younger (48 vs. 68 years-old in Europe) with a relatively higher proportion of patients younger than 40 years old. Although prognosis and outcome of young breast cancer are well studied in developed nations, research evaluating biological characteristics, delivered treatment, and clinical outcomes is very limited in Indonesia. METHODS: We analyzed all breast cancer patients who underwent surgery at Dr. Sardjito Hospital, Indonesia, in 2012-2017. Details of pathology profiles, treatment administrated, and outcomes, as well as reproductive factors among patients younger than 40 years old, were collected and analyzed. Kaplan-Meier curve was used to assess conditional survival based on baseline characteristics. RESULTS: From the total of 1259 breast cancer patients (median age 51 years), 144 (11.4%) were younger than 40 years old (median age 37 years). Of these young patients, 19 (13.2%) were bilateral and 92 (64%) were diagnosed in advanced stages (stages IIIA-C and IV). Median tumor diameter was 5.5 cm and nodal infiltration was present in 73%. Distant metastasis was found in 16% at the time of diagnosis. Moderate and poor differentiation of tumor were 20.8 and 78.5%, respectively, and lymphovascular invasion was found in 90.3%. Around 40% were hormone receptor-positive, 30.6% human epidermal growth factor receptor 2 positive, and 38.2% triple negative. Patients underwent radical surgery in 121 cases (84%) and breast conserving surgery in 7 cases (4.9%). Adjuvant chemotherapy was administrated in 68% and hormonal therapy in 34%. Progression-free survival was significantly shorter in patients with advanced stage, skin and chest wall involvement (T4), positive lymph node infiltration, positive hormonal receptor, and triple negative subtype (log-rank Mantel-Cox tests, p < 0.05). CONCLUSION: We found a high frequency of young breast cancer with biologically more aggressive tumors, late diagnosis, frequent relapse, and poor prognosis. Further actions to improve clinical management and meet psychosocial needs in young breast cancer patients are warranted.

Fighting Global Disparities in Cancer Care: A Surgical Oncology View.

Cancer is the second leading cause of death globally after cardiovascular disease. Long-term cancer survival has improved in the Western world due to early detection and the use of effective combined treatment modalities, as well as the development of effective immunotherapy and drug-targeted therapy. Surgery is still the mainstay for most solid tumors; however, low- and middle-income countries are facing an increasing lack of primary surgical care for easily treatable conditions, including breast, colon, and head and neck cancers. In this paper, a surgical oncology view is presented to elaborate how the Western surgical oncologist can take part in the 'surgical fight' against global disparities in cancer care, and a plea is made to strive for structural solutions, such as a partnership in surgical oncology training. The pros and cons of the use of eHealth and mHealth technologies and education programs for schools and the community are discussed as these create an opportunity to reach a large portion of the population in these countries, at low cost and with high impact.

Long-Noncoding-RNA HOTAIR Upregulation is Associated with Poor Breast Cancer Outcome: A Systematic Review and Meta Analysis.

BACKGROUND: Breast cancer is the most frequent cancer among women worldwide with significant disproportionate mortality rates in developing countries. Although clinical management of breast cancer has been immensely improved, refinement in the prognostic and recurrent markers is still needed. Long non-coding RNAs (lncRNA) HOTAIR has recently been associated with poor outcome and is potentially used as a prognostic marker in breast cancer. METHODS: We comprehensively reviewed studies evaluating lncRNA HOTAIR in association with overall and disease-free survivals in breast cancers. Systematic searches were performed in Pubmed, ProQuest, ScienceDirect, Scopus, Google Scholar, Semantic Scholar, Springer, Nature, Sage Journals, and Wiley databases using combination keywords "long non-coding RNA," "lncRNA," "HOX transcript antisense RNA," "HOTAIR," "breast can-cer," "carcinoma mammae," "prognosis," and "survival." Risk of bias score was used to assess quality of studies, I2 test was conducted to assess heterogeneity. Meta-analysis was performed to compare HOTAIR expression with breast cancer survival rates using STATA v.17 software. RESULTS: Of the total 1,504 screened studies, seven studies were included in the meta-analysis involving 533 patients. High expression of HOTAIR was associated with poor survival rates (pooled HR: 1.69; 95%CI: 1.11-2.59; p=0.015), shorter overall survival (OS) (pooled HR: 1.33; 95%CI: 0.78-2.26; p=0.455), poor disease-free survival (DFS) (pooled HR: 2.40; 95%CI: 1.63-3.53; p<0.001), poor distant metastatic-free survival (MFS) (HR: 1.75; 95%CI: 1.13-2.71; p=0.012). In addition, overexpression of HOTAIR was associated with positive lymph node infiltration (pooled OR: 2.38; 95%CI: 0.53-10.69; p=0.26) and ductal type cancer (pooled OR: 3.27; 95%CI: 1.15-9.30; p=0.03). CONCLUSION: Upregulation of lncRNA HOTAIR is associated with worse DFS aand MFS that can potentially be used as a prognostic marker in breast cancer patients.

Balloon compression-induced spinal cord injury in canines: a large animal model for spinal cord injury research.

Spinal cord injury (SCI) is a life-altering condition that severely impacts an individual's functional capabilities and has significant implications for both the individual and society. Large animal models are crucial for understanding the pathology and biomechanics of SCI. Dogs (Canis lupus familiaris) are promising models for SCI research due to their anatomical and histopathological similarities to humans. Balloon compression is an established method for inducing controlled SCI in canines. In this study, we optimized a balloon compression procedure for inducing SCI in dogs, aiming to develop a reliable model for future in vivo studies. Our methodology successfully induced total motoric loss in canines, observed for seven days, a critical period for therapeutic interventions. Histopathological examinations using Luxol fast blue (LFB) staining revealed total demyelination in intralesional samples, confirming the structural damage caused by balloon compression. We concluded that a balloon compression model at the T10-T11 vertebral level, with an inflated balloon volume of 1.0 ml, induced SCI while minimizing the risk of balloon rupture. Longer duration of compression ensures total paralysis in this model, providing a platform for testing therapeutic interventions during the acute phase of SCI. The canine model generated consistent data and facilitated straightforward observational findings.

MicroRNA Gene Signature for Predicting Mechanisms in Nasopharyngeal Carcinoma: A Case Study on the Potential Application of Circulating Biomarkers.

BACKGROUND AND AIM: Nasopharyngeal Carcinoma (NPC) is an upper respiratory tract cancer prevalent in Southeast Asia and related to chronic EBV infection. microRNAs (miRNAs) regulate gene expression implicated in NPC's carcinogenesis. However, this circulating RNA molecule's role and clinical utility remain unknown. Therefore, this study examined the circulation of miRNAs and their association with clinical data. METHODS: 160 plasma samples of NPC and 80 non-tumor samples were extracted to evaluate and validate the gene expressions. Quantification expression was performed using relative quantification of qPCR analysis level expression methods. The intrinsic cellular roles involving biological signaling in NPC's oncogenesis using Ingenuity Pathways Analysis (IPA) were also used. RESULTS: The results of the quantification significance profiling of NPC samples revealed decreased miR- 29c-3p (fold change 1.16; p<0.05) and increased 195-5p expression (fold change 1.157; p<0.05). Furthermore, the validation of hsa-miR-29c-3p expression on plasma NPC with known tumor vs. non-tumor and significant changes was also performed using a fold change of 4.45 (medians of 31.45 ± 1.868 and 24.96 ± 1.872, respectively; p<0.0005). miR-29c had a 2.14 fold change correlated with T primary status with a median of 31.99±1.319 and 31.35±2.412, respectively (p<0.05). Stage status with fold change 1.99 also had median levels of 31.98±1.105 and 31.21 ± 2.355, respectively (p-value <0.05). Furthermore, the node's status for the lower expression of miR-29c with fold change 1.17 had median levels of 32.78 ± 2.221 and 31.33 ± 1.689, respectively (p-value of 0.7). Bioinformatics analysis established the roles and functions of miR-29 in NPC progression, cell death and survival, cellular development, cellular function, and cell maintenance by inhibiting COL4A, PI3K, VEGFA, JUN, and CDK6. CONCLUSION: Overall, we conclude that decreased miR-29c expression is associated with poor clinical status and might inhibit NPC's five target genes.

Prognostic Value of Vimentin in Triple Negative Breast Cancer Patients Depends on Chemotherapy Regimen and p53 Mutant Expression.

Purpose: To determine the prognostic value of vimentin in triple negative breast cancer (TNBC) patients, specifically in relation to chemotherapy regimen and p53 mutant expression. Patient and Methods: We retrospectively analyzed the association of pre-treatment tumor expression of vimentin with 48-month overall survival (OS) of 72 all stages TNBC patients diagnosed between 2014 and 2018 in relation to chemotherapy regimen and expression of p53 mutant. Vimentin and p53 mutant expressions were examined using immunohistochemistry. Analysis was conducted on all patients collectively, then repeated on two cohorts divided according to the chemotherapy regimen. Sub-analysis was performed to determine the effect of p53 mutant expression on the prognostic value of vimentin. Results: Vimentin was expressed in 43.1% of patients and was not associated with clinicopathologic characteristics. Vimentin was associated with improved 48-month OS in all patients in univariate analysis but not significant in multivariate analysis. When analyzed according to chemotherapy regimen, vimentin was independently associated with improved 48-month OS in patients receiving non-platinum-based chemotherapy (80% vs 15.8%; HR: 0.17, 95% CI: 0.05-0.58, p: 0.005). Other independent prognostic factors include T (HR: 6.18, 95% CI: 1.38-27.7, p: 0.017) and M (HR: 5.64, 95% CI: 1.2-26.33, p: 0.028). On subanalysis, vimentin was significantly associated with improved 48-month OS in patients expressing p53 mutant (69.2% vs 22.2%, p: 0.006) but was not significant in patients not expressing p53 mutant. Conclusion: Vimentin expression was independently associated with improved 48-month OS in TNBC patients treated with non-platinum-based chemotherapy. Expression of p53 mutant significantly affected the prognostic value of vimentin.

Predictors of the conservative management outcomes in patients with lumbar herniated nucleus pulposus: A prospective study in Indonesia.

BACKGROUND: The objective of this study was to identify the predictors of the conservative management outcomes in patients with lumbar herniated nucleus pulposus (HNP). METHODS: A prospective study was conducted between June 2010 and April 2012 in Banda Aceh, Indonesia. Clinical and baseline neurologic examinations such as passive straight leg raising test (SLRT), cross SLRT, and patellar and Achilles reflexes were assessed prior to the conservative management. The patients were evaluated at 2nd, 4th, 8th, 12th and 24th week following commencement of the conservative management. RESULTS: We recruited and followed 171 HNP patients of which 35.7% of them had good outcome. At univariate analysis, patients with more than 12 months duration of complaint, those with dominant radicular pain, severe pain intensity (visual analogue scale 7-10), positive SLRT, positive cross SLRT, and reduced motor power of knee extensors (muscle strength grade 1-4), were associated with poor outcome. Multivariate analysis suggested that patients with dominant radicular type of pain were likely to had poor outcome compared to those with dominant back pain (odd ratio (OR) 10.57 with 95% confidence interval (CI) 1.15-96.93). Patients with reduced motor power of knee extensors also had a higher chance to have poor outcome compared to those who were normal (OR: 10.57; 95% CI: 1.15-96.93). CONCLUSION: Type of pain and the strength of lower extremities could be able to predict the failure of conservative management in patients with lumbar disc herniation. However, further studies with the bigger sample size are warrant to validate our results.

Chemopreventive Effect of Dietary Maranta arundinacea L. Against DMBA-Induced Mammary Cancer in Sprague Dawley Rats Through the Regulation of Autophagy Expression.

BACKGROUND: Breast cancer prevention still needs to be improved. Calorie restriction is thought to prevent breast cancer through the induction of autophagy. Maranta arundinacea L. (MA) has the potential for calorie restriction because it contains high fiber. This research aimed to observe the effect of dietary MA against dimethylbenz(a)anthracene (DMBA)-induced mammary cancer in Sprague Dawley rats related to autophagy. METHODS: Twenty-five Sprague Dawley rats were randomly divided into five groups: 1) control group without DMBA-induced with a standard diet, 2) 20 mg/kg BW of DMBA two times a week for five weeks with a standard diet, 3) DMBA and diet modification with 30% of MA, 4) DMBA and diet modification with 45% of MA, and 5) DMBA and diet modification with 60% of MA. Examination of the nodule was conducted once every week for 22 weeks. Breast tissue/tumor examination underwent histology examination with hematoxylin-eosin. Examinations of immunohistochemical staining against Beclin1, LC3B, and SQSTM1 were conducted to reveal autophagy. The difference of autophagy protein expression was analyzed using One way ANOVA with 95% confidence level and significance set as p<0.05. RESULTS: Cancer was detected in four rats of DMBA standard diet, two rats of 30% MA, one rat of 45% MA. No cancer was detected in the rats of control and rats with 60% of MA group. The Beclin1 expressions showed that the 60% of MA group had the highest score (2.5±0.52) followed by the 45% of MA group (1.87±0.49), control group (1.77±0.11), 30% of MA group (1.28±0.75), and DMBA with standard diet had the lowest score (1.28±0.91). The difference of Beclin1 expressions was statistically significant (p-value=0.03). However, the difference of the LC3B expressions (p-value=0.11) and SQSTM1 expressions (p-value=0.225) were not statistically significant. CONCLUSION: Dietary modifications with MA potentially prevent breast cancer and induce initiation of autophagy.

Cost-Effectiveness Analysis of Two Chemotherapy Regiments FAC vs. Taxane for Operable Breast Cancer Patients in Indonesia.

BACKGROUND: Breast cancer is the deadliest cancer among women worldwide including Indonesia. Both FAC and Taxane-based chemotherapies are often used for patients with early node-positive breast cancer. However, the study regarding the cost-effectiveness of those regiments is still rare. This study aims to analyze the cost-effectiveness of Taxane versus FAC in the Indonesia setting. METHODS: Twenty-four patients with stage I-IIIA breast cancer who had received surgery, FAC or Taxane-based adjuvant chemotherapy, and radiation were included in this study. Health-related quality of life was assessed using INA-BCHRQoL. INA-BCHRQoL was mapped to the EuroQoL 5D (EQ-5D) index calculator to get the utility score. All direct cost was retrieved from electronic medical records and hospital information system. Whereas, a questionnaire was designed to collect information about society cost from patients. ICER was counted to summarize the cost-effectiveness of two chemotherapy regiments (Taxane versus FAC). A sensitivity analysis was done to assess the uncertainty result. RESULTS: The results showed there was no significant difference between the score of quality of life and utility in respondents who received FAC chemotherapy and Taxane-based chemotherapy. However, in terms of cost, Taxane was 6.5 times higher than the FAC group per patient for chemotherapy drugs only. Moreover, the total cost of treatments in Taxane-based chemotherapy was approximately 3.7 times more costly than the counterpart in the FAC arm (p=0.000). Taxane-based chemotherapy dominated with ICER IDR 765.213.092 per QALY gained. Overall, FAC was found more cost-effective compared to the Taxane regiment. CONCLUSION: FAC represents the value of money compared to Taxane-based for breast cancer patients with stage I-IIIA in Indonesia.

The effect of NPWT in wound healing and bacterial count on deep dermal burn injury model: An experimental study.

Background: Sepsis is one of the main causes in burn victim's mortality. The use of negative pressure wound therapy (NPWT) provides an ideal environment to accelerate wound healing. We compare the use of normal saline (NS), intermittent NPWT, continuous NPWT and silver sulfadiazine in wound healing process. Method: This study involved 6 Yorkshire pigs; each pig was induced with 20 burns on the flank area. Burns were divided into 4 treatment groups: NS gauze, intermittent NPWT, continuous NPWT, and silver sulfadiazine dressing. Burns were evaluated on day 1,3,7,14, and 21 for its morphology and bacterial colonization and on day 14 and 21 for the remaining burn surface area. Result: Wound that received NPWT therapy appeared better in both granulation and crust formation. Remaining burn surface area (mm2) on day 14 in NS group, intermittent NPWT, continuous NPWT, and silver sulfadiazine were 107.43 ± 83.43, 178.07 ± 74.83, 146.10 ± 69.1, 126.03 ± 83.22, respectively(p = 0.457); on day 21 in NS group, intermittent NPWT, continuous NPWT, and silver sulfadiazine were 13.16 ± 16.86, 59.49 ± 20.72, 54.79 ± 46.59, 48.95 ± 39.84, respectively(p=0.169). There were no significant differences in each treatment group bacterial colonization(p>0.05). There were no significant correlation between bacterial colonization and remaining burn surface area (p>0.05). Conclusion: While morphologically, the wound in NPWT treatment groups appeared better in granulation and crust formation, the remaining wound surface area and the number of bacterial colonization were not significantly difference compared to standard therapy (silver sulfadiazine and NS gauze). There were no significant correlation between the amount of bacterial colonization and remaining wound surface area on every treatment group.

The Association between Abdominal Obesity, Metabolic Syndrome and Survival Outcomes in Patients with Breast Cancer.

BACKGROUND: Obesity and metabolic syndrome (MetS) have been linked to the risk of developing certain cancers. This study aimed to analyze the association between obesity markers, MetS and survival outcomes of patients with breast cancer. METHODS: This study retrospectively investigated patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-), nonmetastatic breast cancer diagnosed between January 2010 and December 2019. Data on clinical conditions, body mass index (BMI), waist-to-hip ratio (WHR), MetS, time of metastasis and death were collected. RESULTS: A total of 223 breast cancer patient records were eligible for analysis. Obesity (BMI ≥ 25) was found in 38.1% of cases. Abdominal obesity measured as WHR ≥ 0.85 was found in 48.9%. Metabolic syndrome was detected in 56.1% of patients and was associated with older age (OR = 2.196, p = 0.005), postmenopausal status (OR = 2.585, p = 0.001), obesity (OR = 5.684, p = 0.001) and abdominal obesity (OR = 2.612, p = 0.001). Obesity was not associated with poor disease-free survival (DFS) or overall survival (OS), while abdominal obesity was modestly associated with poor DFS (HR = 1.539, p = 0.083) and OS (HR = 3.117; p = 0.019). Multivariate analysis revealed that WHR ≥ 0.85 was independently associated with unfavorable DFS (HR = 1.907, p = 0.027). Patients with MetS had a similar survival rate to those with normal metabolism. CONCLUSION: In Indonesian women with HR+/HER2- breast cancers, obesity and MetS were not associated with poor survival outcomes. The abdominal obesity marker (WHR) was more accurate in predicting unfavorable DFS.

Concentration of serum HER-2/neu as a prognostic factor in locally advanced breast cancer (LABC) and metastatic breast cancer (MBC).

AIM: to determine whether serum HER-2/neu level could be used as a prognostic factor in locally advanced breast cancer (LABC) and metastatic breast cancer (MBC). METHODS: a prospective cohort study was done in LABC and MBC patients in dr. Sardjito Hospital Yogyakarta from April 2006 to March 2008. Serum concentration of HER-2/neu was measured by ELISA done before and after chemotherapy. HER-2/neu expression tissue examination was done by immunohistochemistry. The clinical responses on therapy, survival and progression were recorded. RESULTS: twenty seven cases were obtained. Average concentration of serum HER-2/neu was 21.02 ± 7.1 ng/ml. The level of serum HER-2/neu in LABC was lower than MBC (17.21 ng/ml vs 28.64 ng/ml; p=0.32). Average concentration of serum HER-2/neu in partial responders was 13.20 ng/ml (95% Cl 0.142 - 26.25), stable responders was 19.42 ng/ml (95% Cl -0.255 - 39.09) and 29.35 ng/ml(95% Cl 1.95 - 56.74) in progressors (p=0.468). Patients with better clinical response had a lower average HER-2/neu serum level (16.12 ng/ml vs 29.35 ng/ml; p=0.247). HER-2/neu over expression was found in 40.7% of the tissues, 44% of LABC and 33.3% of MBC tissues (p=0.692). Negative HER-2/neu tissue protein expression had better clinical response (75% vs 45.5% p=0.224), and longer survival (p=0.08). CONCLUSION: neither the expression of HER-2/neu in the tissue nor the level of serum HER-2/neu can be used as clinical prognosis factor on advanced stage breast cancer in our study population.

Obesity, leptin, and deregulation of microRNA in lipid metabolisms: their contribution to breast cancer prognosis.

Obesity and Metabolic Syndrome have been associated with cardiovascular, diabetes and cancer incidence. Obesity is a state of inflammation. There are cross-talks between adipocyte, adipokines, pro-inflammatory cytokines, insulin, leptin, and other growth factors to initiate signals for proliferation, anti-apoptosis, and angiogenesis. Those networks lead to cancer initiation, promotion, progression, and metastasis. Post menopause women with breast cancer commonly have overweight, obesity, and metabolic syndrome, which are previously reported as conditions to be associated with breast cancer prognosis. MicroRNAs (miRNAs), small non-coding RNA that regulate gene expression, are known to play important roles either in metabolic or carcinogenesis process in patients with breast cancer. Some miRNAs expressions are deregulated in persons either with obesity, breast cancer, or breast cancer with co-morbid obesity. This literature review aimed at reviewing recent publications on the role of obesity, leptin, and microRNA deregulation in adverse prognosis of breast cancer. Understanding the influence of deregulated miRNAs and their target genes in patients with breast cancer and obesity will direct more studies to explore the potential prognostic role of obesity in breast cancer from epigenetic points of view.

Concurrent manifestations of Horner's syndrome and esophageal metastasis of breast cancer: case report of a young woman after a period of non-adherence to treatment: a case report.

BACKGROUND: Esophageal involvement and Horner's syndrome are rare manifestations of breast cancer distant metastases that can pose a significant challenge in diagnosis and treatment. In addition to the more aggressive behavior of breast cancer diagnosed in young women, non-adherence to treatment is associated with increased risk of distant metastasis. CASE PRESENTATION: A 36-year-old Javanese woman presented to our institution with dysphagia, hoarseness, and frequent hiccups. In the 6 weeks prior to the current admission, the patient also reported tingling in the neck and shoulder, anhidrosis in the left hemifacial region, and drooping of the upper left eyelid. She was previously managed as tuberculoid laryngitis. Plain X-rays showed burst fractures of the cervical vertebrae and slight pleural effusion. Laryngoscopy revealed bowing of the vocal cords and liquid residue in the vallecula that was reduced upon chin tuck. Esophageal metastasis was confirmed with endoscopy showing thickening of the wall and positive cytology swab with ductal malignant cells. The patient had a history of breast cancer with a period of loss to follow-up of 4 years. CONCLUSIONS: Physicians should consider potential distant metastasis of breast cancer to the esophagus and sympathetic nervous system of the neck particularly in a high-risk woman with presentation of dysphagia and manifestations of Horner's syndrome.

Effect of Primary Systemic Therapy on PD-1, PD-L1, and PD-L2 mRNA Expression in Advanced Breast Cancer.

OBJECTIVE: The association between PD-1, PD-L1, and PD-L2 expression and prognosis has been extensively studied in various cancers but remained controversial in breast cancer. Besides, little is known about the prognostic value of PD-1, PD-L1, and PD-L2 upregulation or downregulation following systemic therapy (chemotherapy and hormonal therapy) in breast cancer. Therefore, we aim to investigate the change of PD-1, PD-L1, and PD-L2 expression in mRNA level after primary systemic therapy in breast cancer patients and its clinical implications. METHODS: Expression of PD-1, PD-L1, and PD-L2 mRNA were measured before-after chemotherapy and hormonal therapy with real-time PCR in 80 advanced breast cancer patients. The correlation between alteration of PD-1, PD-L1, and PD-L2 expression and clinicopathological characteristics as well as overall survival was also statistically analyzed. RESULTS: Chemotherapy and hormonal therapy altered PD-1, PD-L1, and PD-L2 expression in breast cancer with most patients have an increase expression. As much as 57.1%, 62.9% and 60% patients have an increase PD-1, PD-L1, and PD-L2 expression after chemotherapy, while 60%, 60%, and 64% patients have an increase PD-1, PD-L1, and PD-L2 expression after hormonal therapy. Alteration of PD-1, PD-L1, and PD-L2 expression was not correlated with all clinicopathological characteristics. Increase in PD-1, PD-L1, and PD-L2 expression was significantly associated with better OS (p=0.031, p=0.019, and p=0.019 for PD-1, PD-L1, and PD-L2, respectively), which remained significant in multivariate analysis including age, stage, primary systemic therapy, histology grade, subtype and primary tumor histology (HR PD-1 0.5 (95% CI 0.28-0.88) p=0.031; HR PD-L1 0.43 (95% CI 0.24-0.8) p=0.019; HR PD-L2 (95% CI 0.24-0.87) p=0.019).  Conclusion: Expression of PD-1, PD-L1, and PD-L2 in breast cancer patients is mostly enhanced after chemotherapy and hormonal therapy, and the enhancement is associated with good OS. This result revealed the potential of measuring PD-1, PD-L1, and PD-L2 mRNA expression in predicting clinical outcome.