Real-world data on the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab: Turkish oncology group multicenter study.

We aimed to evaluate the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab plus trastuzumab and taxane. We reviewed the medical records of patients who were diagnosed with Human Epidermal Growth Factor Receptor 2 (HER-2) positive metastatic breast cancer and received pertuzumab and then TDM-1 between January 2014 and January 2021 from twenty- five cancer centers. The Kaplan- Meier method estimated progression-free survival (PFS) and overall survival (OS). Additionally, objective response rate (ORR), clinical benefit rate (CBR), and safety were evaluated. One hundred fifty-three patients were included,79.1% of the patients received TDM-1 in the second line, 90.8% had visceral metastasis, and 30.7% had central nervous system involvement. The PFS and OS of TDM-1 were evaluated according to the number of previous lines (on the 2nd line or more than two lines) metastatic sites (visceral and non-visceral) and the presence of central nervous metastasis. In TDM-1 therapy, PFS in second line therapy was ten months (95% CI: 7.7 - 12.2); this was statistically higher than later-line PFS, which was six months (95% CI: 3.3 to 8.6) (p = 0.004). The median OS time was 25 months (95% CI: 21.0 to 28.9) in patients treated with TDM-1 in the second line and 19 months (95% CI: 12.3 to 25.6) in patients who received later than the second line(p = 0.175). There were no significant differences in PFS time of patients with and without visceral and central nervous metastases. Our study showed that TDM-1 was also effective in patients using pertuzumab, contributes significantly to PFS when used in the second line compared to its use in the later line, and does not make any difference in OS.

The effect of education given to hemodialysis patients based on the Roy Adaptation Model on fluid management, symptom control, and quality of life.

This study aimed to determine the effect of fluid management, symptom control, and quality of life on education based on the Roy Adaptation Model. This randomized controlled study was conducted with the participation of 107 patients (53 intervention, 54 control). Data were collected using the "Patient Data Collection Form," "Fluid Control in Hemodialysis Patients Scale," "Dialysis Symptom Index," and "Nottingham Health Profile." The forms were filled out through face-to-face interviews with the patients in the intervention and control groups at the 0th (onset), 1st, and 3rd months. The patients in the intervention group were trained with an education booklet based on the Roy Adaptation Model. The results revealed that the education given according to the Roy Adaptation Model improved the compliance with fluid control, quality of life, and symptom control of hemodialysis patients. It is recommended that education based on the Roy Adaptation Model be systematically used by hemodialysis nurses. The results are limited to the population included in the study, and further research on hemodialysis populations is needed.

Efficacy of Bee Products (Anzer Honey, Pollen and Propolis) in Detection and Healing of Damage Induced by Antidiabetic Drug Vildagliptin/Metformin Hydrochloride in Healthy Human Pancreatic Cells: Cytotoxic, Genotoxic and Biochemical Studies.

BACKGROUND AND OBJECTIVE: Although drugs are powerful therapeutic agents, they have a range of side effects. These side effects are sometimes cellular and not clinically noticeable. Vildagliptin/metformin hydrochloride is one of the most widely used oral antidiabetic drugs with two active ingredients. In this study, we investigated its harmful effects on the metabolic activation system in healthy human pancreatic cells "hTERT-HPNE", and we aimed to improve these harmful effects by natural products. To benefit from the healing effect, we used the unique natural products produced by the bees of the Anzer Plateau in the Eastern Black Sea Region of Turkey. METHODS: Cytotoxic and genotoxic effects of the drug were investigated by different tests, such as MTT, flow cytometry-apoptosis and comet assays. Anzer honey, pollen and propolis were analyzed by gas chromatography/mass spectrometry (G/C-MS). A total of 19 compounds were detected, constituting 99.9% of the samples. RESULTS: The decrease in cell viability at all drug concentrations was statistically significant compared to the negative control (P<0.05). A statistically significant decrease was detected in the apoptosis caused by vildagliptin/metformin hydrochloride with the supplementation of Anzer honey, pollen and propolis in hTERT-HPNE cells (P<0.05). CONCLUSION: This study can contribute to other studies testing the healing properties of natural products against the side effects of oral antidiabetics in human cells. In particular, Anzer honey, pollen and propolis can be used as additional foods to maintain cell viability and improve heal damage and can be evaluated against side effects in other drug studies.

PROPSEA, safety evaluation of palbociclib and ribociclib in older patients with breast cancer: A prospective real-world TOG study.

INTRODUCTION: In this study, the toxicities and management of palbociclib and ribociclib in older patients (≥65 years) with metastatic breast cancer patients were investigated. MATERIALS AND METHODS: Among older patients receiving palbociclib and ribociclib, Geriatric 8 (G8) and Groningen Frailty Index were used to evaluate frailty status. Dose modifications, drug withdrawal and other serious adverse events (SAEs) were recorded and analyzed according to baseline patient characteristics. RESULTS: A total of 160 patients from 28 centers in Turkey were included (palbociclib = 76, ribociclib = 84). Forty-three patients were ≥ 75 years of age. The most common cause of first dose modification was neutropenia for both drugs (97% palbociclib, 69% ribociclib). Liver function tests elevation (10%) and renal function impairment (6%) were also causes for ribociclib dose modification. Drug withdrawal rate was 3.9% for palbociclib and 6% for ribociclib. SAEs were seen in 11.8% of those taking palbociclib and 15.5% of those on riboclib. An ECOG performance status of ≥2 and being older than 75 years were associated with dose reductions. Severe neutropenia was more common in patients with non-bone-only metastatic disease, those receiving treatment third-line therapy or higher, coexistance of non-neutropenic hematological side effects (for ribociclib). Neutropenia was less common among patients with obesity. DISCUSSION: Our results show that it can be reasonable to start palbociclib and ribociclib at reduced dose in patients aged ≥75 years and/or with an ECOG performance status ≥2.

Prognostic significance of immunhistochemical axl expression in pancreas ductal adenocarcinomas.

Introduction and Aim: Pancreas Ductal Adenocarcinomas (PDACs) are among the leading causes of cancer-related death. Tyrosine kinase receptors (TKRs) are responsible for cell plasticity, chemoresistance, immunosuppression and metastasis potential. Axl is a receptor of the TKR family, and it has come to the fore in cancer treatment in the last decade. This study aimed to investigate the relationship of immunohistochemical Axl expression with histological features and its prognostic importance in PDACs. Materials and Methods: Fifty-three patients who were operated on for PDAC between 2006-2017 were evaluated retrospectively. Features of tumors; size, lymphovascular invasion (LVI), perineural invasion (PNI), resection margin (RM), lymph node metastasis (LNM), differentiation, tumor-infiltrating lymphocyte, stage and overall survival were recorded. Immunohistochemically, membranous and or cytoplasmic staining was considered positive for Axl. Statistically, Pearson Chi-Square, Cox regression and Kaplan Mayer tests were used in the SPSS 21.0 program. Results: Axl was positive in 28 patients (52.8%). Axl positivity was found to be associated with the presence of LVI (P = 0.009) and LNM (P = 0.002) and was an independent prognostic factor in short survival (P = 0.006). Conclusion: It was found that increased expression of Axl, which is known to increase EMT-mediated metastasis in carcinogenesis, may be an indicator of local spread and poor prognosis in PDAC patients. In this respect, it can be promising as a targeted molecule in PDAC patient's individualized treatments.

Effects of Perioperative Hypothermia on Extubation, Recovery Time, and Postoperative Shivering in Breast Surgery.

Women undergoing breast surgery seem to be under the risk for hypothermia (central body temperature <36°) due to the uncertainty caused by the preoperative preparation time and the variety of operations, leading to neglect of warming precautions. The study examines the perioperative hypothermia (PH) in breast surgery and the relationships between the depth of decrease in body temperature and individual or clinical variables. This prospective, cross-sectional, observational study includes 120 female patients 18-65 years of age who were given general anesthesia for breast surgery. The incidence of hypothermia was 68.1%. The given patients were discriminated as body temperature <36°, hypothermia was significantly related with lower weight, body mass index, American Society of Anesthesiology (ASA) score, baseline body temperatures, higher extubation, and recovery times. When patients' temperature decreases by >1 or 1.5°, lower age and longer durations of operation and anesthesia were also significant variables. The incidence of shivering is quite high at temperatures below 36°C or at 1 and 1.5°C reductions from baseline (72.7%, 84%, 94.1%, respectively). Body temperature changes of the patients had no effect on nausea-vomiting and pain scores. It turned out that the incidence of PH and shivering is high in women who underwent breast surgery. We think that the depth of decrease in body temperature should be taken into account when evaluating the predictors or clinical consequences of hypothermia, except for the 36°C limit for body temperature.

The effect of low back and neck pain on posture, burnout, and quality of life in formal caregivers of children with disabilities and the elderly.

BACKGROUND: Caregiving, which is often described as a stressful job due to the patience and dedication it requires, affects the physical and mental health of the employees of the profession due to various factors. AIMS: This study was conducted to investigate the effects of lower back and neck pain on posture, burnout level, and quality of life of the formal caregivers of children with disability and the elderly. METHODS: The study included 64 formal caregivers of children with disability and the elderly. The socio-demographic characteristics of the participants were recorded. The Oswestry Disability Index, the Neck Disability Index, the Maslach Burnout Inventory, and the Short Form-36 were used to evaluate low back pain, neck pain, burnout levels, and quality of life, respectively. Participants' spinal posture values were measured with the Spinal Mouse device. RESULTS: When the groups were combined and examined, it was found that neck pain caused changes in the spinal posture (p < 0.05) and that low back pain did not affect spinal posture (p > 0.05). Also, low back and neck pain had an increasing effect on emotional burnout and desensitization and a decreasing effect on the quality of life (p < 0.05). CONCLUSIONS: In this study, it was observed that low back and neck pain experience has negative effects on individuals' posture, burnout levels, and quality of life.

The Oncologic Safety of Sentinel Lymph Node Biopsy in Patients with Node-Positive Breast Cancer with Complete Response to Neoadjuvant Chemotherapy: A Single-Center Experience.

Objective: To evaluate the efficiency and safety of sentinel lymph node biopsy (SLNB) in patients with breast cancer with complete response to neoadjuvant chemotherapy (NAC). Methods: Ninety-two consecutive (T1-4 and N1-2) patients with breast cancer who had pathologic and/or clinical and radiologic axillary lymph node involvement were included. All patients received NAC. Patients with a clinical and radiologic complete response in the axilla after NAC underwent SLNB. Pathologic complete response (ypCR) was defined as the absence of residual invasive and in situ cancer, and near-complete response (ypNCR) represented in situ and/or ≤ 1 mm residual tumor in the breast and/or presence of malignant cell clusters (≤0.2 mm) and/or micrometastases (≤2.0 mm) in the axillary lymph nodes (ALN) (ypTis/T1mi, ypN0i+/pN1mi). Results: The mean age of the 92 patients was 49.6 ± 10.3 years and the mean follow-up was 34.0 ± 17.8 months. With respect to breast tumors, 23 (25.0%) patients had complete and 14 (15.2%) had a near-complete response to NAC. Complete response in ALN was obtained in 39 (42.4%) patients and near-complete in six (6.5%) patients. The overall survival of the 33 patients who achieved ypCR and ypNCR was 100% and the remaining 59 patients with partial or no response to NAC was 83.1% at a mean follow-up of 34 months (p=0.063). Conclusions: In this study, no event developed in cases with ypCR and ypNCR in the breast and axilla. The persistence of the same results in long-termfollow-ups may enable the use of ypNCR as a positive prognostic marker in addition to ypCR.

A new bio-active asymmetric-Schiff base: synthesis and evaluation of calf thymus DNA interaction, topoisomerase IIα inhibition, in vitro antiproliferative activity, SEM analysis and molecular docking studies.

In this paper, the asymmetric-Schiff base 2-(4-(2-hydroxybenzylideneamino)benzylideneamino)benzoic acid (SB-2) was newly synthesized and characterized by various spectroscopic methods. The interaction of SB-2 with calf thymus DNA was investigated by UV-vis, fluorescence spectroscopy and molecular docking methods. It was determined that SB-2 effectively binds to DNA via the intercalation mode. DNA electrophoretic mobility experiments displayed that topoisomerase IIα could not cleave pBR322 plasmid DNA in the presence of SB-2, confirming that the Schiff base acts as a topo II suppressor. In the molecular docking studies, SB-2 was found to show an affinity for both the DNA-topoisomerase IIα complex and the DNA. In vitro antiproliferative activity of SB-2 was screened against HT-29 (colorectal) and HeLa (cervical) human tumor cell lines by MTT assay. SB-2 diminished the cell viability in a concentration- and incubation time-dependent manner. The ability of SB-2 to measure DNA damage in tumor cells was evaluated with cytokinesis-block micronucleus assay after incubation 24 h and 48 h. Light and scanning electron microscopy experiments of tumor cells demonstrated an incubation time-dependent increase in the proportion of apoptotic cells (nuclear condensation and apoptotic bodies) suggesting that autophagy and apoptosis play a role in the death of cells. Based on the obtained results, it may be considered that SB-2 is a candidate for DNA-targeting antitumor drug.Communicated by Ramaswamy H. Sarma.

Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study.

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice.  Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

In Vitro Transcriptome Analysis of Cobalt Boride Nanoparticles on Human Pulmonary Alveolar Cells.

Nanobiotechnology influences many different areas, including the medical, food, energy, clothing, and cosmetics industries. Considering the wide usage of nanomaterials, it is necessary to investigate the toxicity potentials of specific nanosized molecules. Boron-containing nanoparticles (NPs) are attracting much interest from scientists due to their unique physicochemical properties. However, there is limited information concerning the toxicity of boron-containing NPs, including cobalt boride (Co2B) NPs. Therefore, in this study, Co2B NPs were characterized using X-ray crystallography (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX) techniques. Then, we performed 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, and neutral red (NR) assays for assessing cell viability against Co2B NP exposure on cultured human pulmonary alveolar epithelial cells (HPAEpiC). In addition, whole-genome microarray analysis was carried out to reveal the global gene expression differentiation of HPAEpiC cells after Co2B NP application. The cell viability tests unveiled an IC50 value for Co2B NPs of 310.353 mg/L. The results of our microarray analysis displayed 719 gene expression differentiations (FC ≥ 2) among the analyzed 40,000 genes. The performed visualization and integrated discovery (DAVID) analysis revealed that there were interactions between various gene pathways and administration of the NPs. Based on gene ontology biological processes analysis, we found that the P53 signaling pathway, cell cycle, and cancer-affecting genes were mostly affected by the Co2B NPs. In conclusion, we suggested that Co2B NPs would be a safe and effective nanomolecule for industrial applications, particularly for medical purposes.

The Importance of the Pathological Perspective in the Management of the Invasive Lobular Carcinoma.

Background: Invasive lobular carcinomas (ILC) account for 10-15% of all breast cancers and are the second most common histological form of breast cancer. They usually show a discohesive pattern of single cell infiltration, tend to be multifocal, and the tumor may not be accompanied by a stromal reaction. Because of these histological features, which are not common in other breast tumors, radiological detection of the tumor may be difficult, and its pathological evaluation in terms of size and spread is often problematic. The SSO-ASTRO guideline defines the negative surgical margin in breast-conserving surgeries as the absence of tumor detection on the ink. However, surgical margin assessment in invasive lobular carcinomas has not been much discussed from the pathological perspective. Methods: The study included 79 cases diagnosed with invasive lobular carcinoma by a Tru-cut biopsy where operated in our center between 2014 and 2021. Clinicopathological characteristics of the cases, results of an intraoperative frozen evaluation in cases that underwent conservative surgery, the necessity of re-excision and complementary mastectomy, and consistency in radiological and pathological response evaluation in cases receiving neoadjuvant treatment were questioned. Results: The tumor was multifocal in 37 (46.8%) cases and single tumor focus in 42 (53.2%) cases. When the entire patient population was evaluated, regardless of focality, mastectomy was performed in 27 patients (34.2%) and breast-conserving surgery (BCS) was performed in 52 patients (65.8%). Of the 52 patients who underwent BCS, 26 (50%) required an additional surgical procedure (cavity revision or completion mastectomy). There is a statistical relationship between tumor size and additional surgical intervention (p < 0.05). BCS was performed in 7 of 12 patients who were operated on after neoadjuvant treatment, but all of them were reoperated with the same or a second session and turned to mastectomy. Neoadjuvant treatment and the need for reoperation were statistically significant (p < 0.05). Additional surgical procedures were performed in 20 (44.4%) of 45 patients in BCS cases who did not receive neoadjuvant therapy. Conclusions: Diagnostic difficulties in the intraoperative frozen evaluation of invasive lobular carcinoma are due to the different histopathological patterns of the ILC. In our study, it was determined that large tumor size and neoadjuvant therapy increased the need for additional surgical procedures. It is thought that the pathological perspective is the determining factor in order to minimize the negative effects such as unsuccessful cosmesis, an additional surgical burden on the patient, and cost increase that may occur with additional surgical procedures; for this reason, new approaches should be discussed in the treatment planning of invasive lobular carcinoma cases.

Gastrointestinal Tract Metastases of Invasive Lobular Carcinoma of the Breast: An Immunohistochemical Survey Algorithm.

Invasive lobular carcinoma (ILC) accounts for almost 15% of all breast carcinomas. The potential of ILC to metastasize to the gastointestinal system is significantly greater than that of invasive ductal carcinoma. Gastric metastasis occurred in the ninth year of the follow-up in a patient who was operated on the right breast due to ILC. The patient was investigated for simultaneous masses in the stomach and colon, and a random mass was found in her right breast.

Investigation of the levels of low back pain, depression, and burnout of the personnel providing formal care for children with disability and elderly individuals.

OBJECTIVES: The aim of the study was to investigate and compare the low-back pain, depression, and burnout levels among formal caregivers of elderly individuals and children with disability. METHODS: This descriptive and cross-sectional study included 29 caregivers of children with disabilities (Group 1) and 26 caregivers of elderly individuals (Group 2). The sociodemographic characteristics of the participants were questioned. The part of low back pain in the Standardized Nordic Musculoskeletal Questionnaire was used to estimate of low back pain. Beck Depression Inventory and Maslach Burnout Inventory were used to evaluate the levels of depression and burnout, respectively. In analysis, percentage values, mean, standard deviation, frequency, and t-test for comparative statistics and Chi-square and Fisher Exact test for categorical variables were used. RESULTS: There was a significant difference between the two groups only for the frequency of pain (p=0.039). There was a significant difference in depression levels between the groups (p=0.001) and no difference in the burnout level of the among groups (emotional exhaustion p=0.21; depersonalization p=0.95; and personal achievement p=0.066). CONCLUSION: It was observed that the disabled and elderly care personnel included in this study similarly experienced moderate burnout, and they also had similar complaints in terms of low back pain, except for the frequency of pain. It was found that the depression levels of the disabled child caregivers were higher than the elderly caregivers. As a result, it has been seen that care work can cause both physical and psychosocial problems in both groups.

Health perceptions and obesity awareness of nursing students.

BACKGROUND: Obesity is a chronic disease that is a global problem. Individuals' perceptions of what health and a healthy lifestyle constitute have an important role in preventing obesity. PURPOSE: This study aimed to determine the relationship between nursing students' health perceptions and obesity awareness. METHODS: This descriptive cross-sectional study was conducted with nursing students (n = 242) between December 20, 2019 and March 20, 2020 in the XXXXX School of Health. A student information form, health perception scale, and obesity awareness scale were used to collect the data. RESULTS: The average total score of the obesity awareness scale was 3.14 ± 0.36, and the average total score of the health perception scale was 38.48 ± 6.65. CONCLUSIONS: Overall, the students perceived that health status was more associated with concepts such as chance and destiny. It is recommended that students' health perceptions be improved.

The effectiveness and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2-positive breast cancer: Turkish Oncology Group study.

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.

The Significance of Tumor Budding and Immunohistochemical Axl Expression in Gallbladder Adenocarcinomas

Background: Tumor budding is a histopathological finding that is accepted as an indicator of epithelial-mesenchymal transformation in many solid tumors. Axl is a Receptor Tyrosine Kinase (RTK) family member and contributes to epithelial-mesenchymal transformation. It has been reported that its overexpression in various solid cancer cells is associated with a poor prognosis. It is claimed that Axl RTK may be the targeted molecule in treating some cancers due to its location in the cell membrane. Aims: To investigate the relationship between immunohistochemical (IHC) Axl expression with tumor budding on the histopathological level and their prognostic significance in patients with gallbladder carcinoma. Thus, it is aimed to contribute to the emergence of a molecular option for targeted, personalized therapy in these patients. Study Design: A retrospective cross-sectional study. Methods: Thirty-eight gallbladder cancer patients who underwent surgery between 2000 and 2017 were included in the study. The expressions of Axl RTK in tumor tissues were evaluated by the IHC method. Demographic data (age, sex) of patients, histopathological features (size, growth pattern), tumor differentiation, pathological T staging, lymphovascular invasion, perineural and serosal invasion, surgical margin, tumor infiltrated lymphocyte, and tumor budding were examined. The tumor budding of the tumor was made according to the International Tumor Budding Consensus Conference and was classified as low (0-4 buds), intermediate (5-9 buds), high (≥ 10 buds). The relationship between clinical pathologic features, the survival rate, and Axl expression was analyzed with Person's chi-square, Cox regression tests, and the Kaplan-Meier method. Results: Tumor budding was determined as low in 12, intermediate in 10, and high in 16 cases. The increased degree of tumor budding was associated with focal-diffuse Axl expression (p = 0.018), infiltrative growth patterns (p = 0.031), poor differentiation (p = 0.006), advanced pathological stage (p = 0.002), and serosal (p = 0.040), perineural (p = 0.008), and lymphovascular invasion (p < 0.0001). Overall survival time was shorter in patients with intermediate to high tumor budding compared with those with low tumor budding (p = 0.011). Conclusion: Axl expression appears to be associated with tumor budding capacity, which may be a poor prognostic criterion for patients with gallbladder cancer. It may be a good target to prevent tumor budding to reduce tumor invasion and metastasis.

Molecular Genetics and Cytotoxic Responses to Titanium Diboride and Zinc Borate Nanoparticles on Cultured Human Primary Alveolar Epithelial Cells.

Titanium diboride (TiB2) and zinc borate (Zn3BO6) have been utilized in wide spectrum industrial areas because of their favorable properties such as a high melting point, good wear resistance, high hardness and thermal conductivity. On the other hand, the biomedical potentials of TiB2 and Zn3BO6 are still unknown because there is no comprehensive analysis that uncovers their biocompatibility features. Thus, the toxicogenomic properties of TiB2 and Zn3BO6 nanoparticles (NPs) were investigated on human primary alveolar epithelial cell cultures (HPAEpiC) by using different cell viability assays and microarray analyses. Protein-Protein Interaction Networks Functional Enrichment Analysis (STRING) was used to associate differentially expressed gene probes. According to the results, up to 10 mg/L concentration of TiB2 and Zn3BO6 NPs application did not stimulate a cytotoxic effect on the HPAEpiC cell cultures. Microarray analysis revealed that TiB2 NPs exposure enhances cellular adhesion molecules, proteases and carrier protein expression. Furthermore, Zn3BO6 NPs caused differential gene expressions in the cell cycle, cell division and extracellular matrix regulators. Finally, STRING analyses put forth that inflammation, cell regeneration and tissue repair-related gene interactions were affected by TiB2 NPs application. Zn3BO6 NPs exposure significantly altered inflammation, lipid metabolism and infection response activator-related gene interactions. These investigations illustrated that TiB2 and Zn3BO6 NPs exposure may affect different aspects of cellular machineries such as immunogenic responses, tissue regeneration and cell survival. Thus, these types of cellular mechanisms should be taken into account before the use of the related NPs in further biomedical applications.

Prognostic Value of Receptor Change After Neoadjuvant Chemotherapy in Breast Cancer Patients.

Objective: The aim of this study was to investigate the relationship between hormone receptors (HR) and human epidermal growth factor receptor 2 (HER-2) discordance with prognosis, before and after neoadjuvant chemotherapy (NAC) in breast cancer patients. Materials and Methods: Histopathological data of 142 breast cancer patients attending a single center between 2001 and 2018 and were operated after NAC were evaluated retrospectively. Results: The median (range) age of patients was 58 (32-69) years. In patients who underwent Tru-cut biopsy before NAC, 77 patients were ER+, 30 were ER (-), 73 were PR (+), 33 were PR-, 14 were HER-2 (+), and 94 patients were HER-2 (-). In terms of ER change, five patients were found to have changed status and 85 had no receptor change. The mean overall survival of patients with receptor changes was 31 months against 60 months in patients with no receptor changes, which was not significant (p = 0.351). In sub-group analysis of patients undergoing receptor change, the ER (+) → (-) group had significantly shorter survival (p = 0.003). For PR change, mean survival was 38 months in seven patients with a receptor change and 59 months in 87 patients without a receptor change, which was not significant (p = 0.603). Sub-group analysis of PR status change showed that survival was significantly shorter in the PR (+) → (-) group (p = 0.012). Conclusion: These results suggest there is a need for reassessment of HR and HER-2 status in surgical samples from patients following NAC, and that NAC-induced changes in the HR state may be used as a prognostic factor.

The effect of upper limb lymphedema in posture of patients after breast cancer surgery.

BACKGROUND: Upper limb lymphedema is one of the complications following breast cancer-related surgery. It is a fact that there are alterations in posture of the trunk following surgery, however, there is not much data on whether upper limb lymphedema has any effect on body posture. OBJECTIVES: The main purpose of the study was to investigate the effect of upper limb lymphedema in the trunk posture and spine mobility of patients following breast cancer surgery. METHODS: Twenty-seven women with lymphedema and 29 women without lymphedema with mastectomy or breast-conserving surgery participated in the study. Posture was evaluated by the New York Posture Rating Chart and spinal stability and thoracic mobility were evaluated by the Spinal Mouse device. RESULTS: Posture and spine posture scores were significantly higher in the without lymphedema group (p= 0.004; 0.041; respectively). There was a significant difference between the groups in terms of lateral (p< 0.001) and posterior (p< 0.001) view of shoulders, spine (p= 0.027), upper (p< 0.001) and lower back (p= 0.009), and trunk postures (p= 0.001). CONCLUSIONS: Body posture and spine are more affected due to upper limb lymphedema following breast cancer surgery. Alterations of posture mainly occur on shoulders, spine, upper and lower back, and trunk, but not on head and neck postures.