How to survive aneuploidy.

Aneuploidy, or an abnormal number of chromosomes, adversely affects cell growth, but it is also linked with cancer and tumorigenesis. Now, Torres et al. (2010) help to resolve this paradox by demonstrating that aneuploid yeast cells can evolve mutations in the proteasome protein degradation pathway that alleviate imbalances in protein production and increase the cell's proliferative capacities.

Isolation, identification, and in vitro probiotic characterization of forty novel Bifidobacterium strains from neonatal feces in Erzurum province, Türkiye.

BACKGROUND: Neonatal feces are one of the most important sources for probiotic isolation. The purpose of this study was the isolation and identification of Bifidobacterium spp. from neonatal feces and the evaluation of in vitro probiotic properties of strains including safety tests. RESULTS: A total of 40 isolates were obtained from 14 healthy newborns' feces in Erzurum province, Türkiye. By their rep-PCR patterns and 16S rRNA gene sequences, isolates were identified as 26 Bifidobacterium breve and 14 Bifidobacterium longum. Fifteen of the isolates tolerated bile salts and showed high resistance to simulated gastric juice. Isolates exhibited varying rates of auto-aggregation and hydrophobicity. In addition, most of the isolates displayed antibacterial activity against Escherichia coli O157:H7, Staphylococcus aureus ATCC 29213, Salmonella Typhimurium RSHMB 95091, and Pseudomonas aeruginosa ATCC 9027. However, only one strain showed bile salt hydrolase activity and two strains showed the ability to produce H2O2. Bifidobacterium strains were generally sensitive to the tested antibiotics and lacked kanamycin, gentamicin, and streptomycin resistance genes, and hemolytic and DNAse activities. On the other hand, it was determined that five strains had various virulence genes including gelE, esp, efaAfs, hyl, and ace. CONCLUSION: Results of the present study suggested that B. longum BH28, B. breve BH4 and B. breve BH5 strains have the potential as probiotic candidates for further studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

Prognostic value of computed tomography associated body composition measurement changes in metastatic colorectal cancer patients.

BACKGROUND: Sarcopenia is associated with poor prognosis in metastatic colorectal cancer (mCRC) patients. PURPOSE: To investigate the prognostic value of body composition measurement changes measured by computed tomography (CT) in mCRC patients. MATERIAL AND METHODS: The abdominal skeletal muscle density (SMD) and skeletal muscle (SMI) indices, as well as the visceral (VATI) and subcutaneous fat tissue (SATI) indices, were calculated by automatic segmentation method on the abdominal CT images obtained before (n = 71) and after chemotherapy (n = 52). Skeletal muscle gauge (SMG = SMD × SMI) was calculated. We calculated the percentage change of body composition measurements with respect to the first measurements. The cutoff value for the change in SMG was calculated by receiver operating characteristic analysis. Kaplan-Meier and Cox regression analyses were performed to calculate the prognostic value of age, gender, tumor location, metastasis site and carcinoembriogenic antigen (CEA) elevation, hypoalbuminemia, body mass index classification, presence of sarcopenia and SMG changes in terms of overall survival. RESULTS: There was a significant association between SMG change and mortality (P = 0.037). According to survival analyses, highly decreased SMG, hypoalbuminemia and CEA variables of the patients were the significant factors (P < 0.001, P = 0.015 and P = 0.019, respectively). According to multivariate regression analysis, hypoalbuminemia (P = 0.004, hazard ratio = 3.60) and highly decreased SMG (P < 0.001, hazard ratio = 14.98) were found to be significant prognostic factors together. CONCLUSION: In mCRC patients, hypoalbuminemia and highly decreased SMG are significant prognostic factors for overall survival. Therefore, we suggest that the change in SMG calculated in follow-up images should also be evaluated in the prognosis estimation of this patient group.

Reshaping Treatment Paradigms for Advanced Renal Cell Cancer Patients and Improving Patient Management : Optimal Management for Renal Cell Cancer Patients.

OPINION STATEMENT: The treatment of renal cell carcinoma (RCC) is one of the great success stories in the field of oncology, which was revolutionized with the development of therapies aimed at disrupting crucial pathways. Tumor biology of RCC has provided insight into the disease through elucidation of the role of vascular endothelial growth-factor (VEGF) and the mammalian target of rapamycin (mTOR). Targeted agents against VEGF and mTOR, as well as agents targeting relevant immunomodulatory pathways, have shown clinical benefit for advanced disease. The targeted agents are highly effective in achieving a response and survival, particularly in high-risk patients. These include the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) axitinib and cabozantinib, and programmed cell death 1 protein (PD-1) immune checkpoint inhibitors (ICI) nivolumab and pembrolizumab. There is a wealth of evidence investigating different therapeutic options and combinations for first-line treatment of advanced RCC including the CheckMate 214 study, KEYNOTE-426, JAVELIN Renal 101, and CheckMate 9ER. Dual ICI and combination agents targeting the programmed cell death protein 1/programmed cell death protein ligand 1 (PD1/PDL1) and VEGF, began to demonstrate superiority over previously accepted standards in advanced clear-cell RCC. Data from a number of clinical studies are available to help physicians with evidence-based decisions for the sequence of second-line and future treatments for patients with progressive RCC. In this review, we focus on essentials for clinicians treating patients with clear-cell RCC.

CDK4/6 inhibitors: mechanisms of resistance and potential biomarkers of responsiveness in breast cancer.

Hormone receptor (HR)-positive, HER2-negative tumors represent the most common form of metastatic breast cancer (MBC), and endocrine therapy has been the mainstay treatment for several decades. Recently, a novel drug class called CDK4/6 inhibitors in combination with endocrine therapy have remarkably improved the outcome of patients with HR-positive, HER2-negative MBC by targeting the cell cycle machinery and overcoming aspects of endocrine resistance. Several potential cell-cycle-specific and nonspecific mechanisms of resistance to CDK4/6 inhibitors have been reported in recent studies. This review discusses potential resistance mechanisms to CDK4/6 inhibitors, the use of biomarkers to guide treatment for HR-positive, HER2-negative MBC and possible approaches to overcome resistance to CDK4/6 inhibitors.

Approximately 70% of breast cancers are hormone receptor (HR)-positive. A CDK4/6 inhibitor combined with endocrine therapy is the first-line standard of care for patients with HR-positive, HER-2 negative advanced breast cancer. Markers to predict the efficacy of CDK4/6 inhibitors in HR-positive, HER2-negative advanced breast cancer are limited. In this review, we summarize the use of CDK4/6 inhibitors in breast cancer, as well as possible approaches to overcome resistance to CDK4/6 inhibitors.

Investigation of anxiety sensitivity levels of cancer patients in terms of COVID-19 vaccine: a cross-sectional study.

INTRODUCTION: Our study's purpose was to investigate the viewpoints of cancer patients who had not yet been vaccinated. Cancer patients usually cannot get every vaccine because their immunity is low. For this reason, we aimed to detect their anxiety and curiosity for new vaccines for a new disease. METHODS: The goal of this descriptive cross-sectional study was to investigate cancer patients' perceptions of COVID vaccination. Over 18 years of age who have not yet been vaccinated for COVID-19 and who agreed to participate were included in the study. We applied three questionnaires between May and June 2021, one of them was prepared by us; the other two questionnaires were The State-Trait Anxiety Inventory (STAI) form and Anxiety Sensitivity index to a total of 497 participants. Chi-square, Spearmen correlation test, and multivariable multinomial logistic regression tests were used when comparing. RESULTS: Our participants' ages were between 21 and 88, with a mean age of 61.38 (SD = 11.68), 48.6% (n = 251) of the participants were female. We discovered that 79.1% (n = 408) of respondents were not afraid of getting the COVID-19 vaccine. 27.7% (n = 143) of these patients were concerned about the COVID-19 vaccine's adverse effects, and 24.2% (n = 125) were afraid of its side effects with their treatments. 91.1% (n = 470) of the patients did not know which vaccine they would have and the type of the vaccine. Since the anxiety level is generally higher in women, anxiety scores were also higher in cancers seen in women, such as breast and ovarian cancer. Of course, in parallel with this, anxiety scores were lower in prostate cancers. Special patient groups should not be neglected during this vaccine season, and their concerns should be addressed. When a new vaccine is found, it can have long-term effects, which should not be ignored.

Optimal Treatment for Patients with Oligometastatic Prostate Cancer.

Oligometastatic prostate cancer (PCa) can be defined as cancer with a limited number of metastases, typically fewer than 5 lesions, and involves lesions contained within the axial versus the appendicular skeleton. Patients can present with de novo oligometastatic, oligorecurrent, or oligoprogressive PCa. Oligometastatic PCa patients demonstrate considerable improvements in survival outcomes, with a better prognosis than patients with extensive metastatic disease. However, the management of patients that present with nonsymptomatic oligometastatic PCa remains difficult. In the oligometastatic setting, the benefit of local therapies such as prostatectomy and radiotherapy on survival outcomes is an intriguing topic; however, their impact on oncological outcomes is still unknown.

Catalytic assembly of the mitotic checkpoint inhibitor BubR1-Cdc20 by a Mad2-induced functional switch in Cdc20.

The mitotic checkpoint acts to maintain chromosome content by generation of a diffusible anaphase inhibitor. Unattached kinetochores catalyze a conformational shift in Mad2, converting an inactive open form into a closed form that can capture Cdc20, the mitotic activator of the APC/C ubiquitin ligase. Mad2 binding is now shown to promote a functional switch in Cdc20, exposing a previously inaccessible site for binding to BubR1's conserved Mad3 homology domain. BubR1, but not Mad2, binding to APC/C(Cdc20) is demonstrated to inhibit ubiquitination of cyclin B. Closed Mad2 is further shown to catalytically amplify production of BubR1-Cdc20 without necessarily being part of the complex. Thus, the mitotic checkpoint is produced by a cascade of two catalytic steps: an initial step acting at unattached kinetochores to produce a diffusible Mad2-Cdc20 intermediate and a diffusible step in which that intermediate amplifies production of BubR1-Cdc20, the inhibitor of cyclin B ubiquitination, by APC/C(Cdc20).

Understanding relevant immune mechanisms in gastrointestinal oncology.

Rapid and successful drug development has resulted in multiple treatment options for gastrointestinal cancer, requiring careful decision making for individual patients. The general theme in modern immunology is that the field is moving beyond establishing the fundamental principles of immune response mechanisms to applying these propositions to understand human diseases and develop new therapies. Immunotherapy has contributed enormously to cancer treatments with a virtual explosion in novel therapeutics including checkpoint inhibitors and other recently developed immunomodulators and the development of novel therapeutic approaches. Although the majority of gastrointestinal (GI) cancers are generally considered poorly immunogenic, clinical trials have revealed that some of the patients with various gastrointestinal cancers are highly responsive to immune checkpoint inhibition-based therapies. We paid special attention to the clinical relevance of immunology and emphasized how newly developed therapies work, including what their strengths and pitfalls are. This review aims to enhance the interest of practitioners in the many specialties and subspecialties that the discipline influences and to assist them in understanding this increasing complexity.

Second Primary Tumors in Patients with Gastrointestinal Stromal Tumors: A Single-Center Experience.

Background and Objectives: In this study, we investigated the frequency and type of second primary malignant tumors (SPMTs) accompanying gastrointestinal stromal tumors (GISTs), patient and tumor characteristics, and follow-up and survival data. Materials and Methods: We included 20 patients with SPMTs from a total of 103 patients with GISTs in a single center in Turkey. At the time of GIST diagnosis, patient age, sex, presentation symptoms, localization, pathological features of the tumor, stage, recurrence risk scoring for localized disease, treatments received, time of SPMT association, follow-up times, and survival analysis were recorded for each patient. Localization, histopathology, and stage of SPMT accompanying GISTs were also recorded accordingly. Results: SPMT was detected in 19.4% of patients with GISTs. Of the patients, 50% were men and 50% were women. The mean age at the time of diagnosis of GIST was 63.8 ± 10.81 years (range: 39-77 years). Of the GISTs, 60% were localized in the stomach, 25% in the small intestine, and 70% were at low risk. Of the SPMTs, 60% were in the gastrointestinal system. SPMTs were diagnosed as synchronous with GISTs in 50% of the patients. The mean follow-up period of the patients from the diagnosis of GIST was 45.6 (0.43-129.6) months. When the data were finalized, 5% died due to GIST, 35% died due to SPMT, and 15% died due to non-disease-related causes. Conclusions: SPMT was detected in 19.4% of patients with GISTs. GISTs were frequently located in the stomach, and most of them were at low risk. The most common SPMTs were gastrointestinal system tumors, and their coexistence was found to be synchronous. Most patients died due to SPMT during follow-up.

Pazopanib-Induced Hepatotoxicity in an Experimental Rat Model.

Pazopanib is an effective treatment for advanced renal cell carcinoma and soft tissue sarcoma. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. The aim of the present study was to evaluate the effect of pazopanib on the liver in an experimental rat model. Sixteen Wistar albino rats were divided into 3 groups: experimental toxicity was induced with pazopanib (10 mg/kg) administered for 28 days (group 2) or 56 days (group 3) orally by gavage. Group 1 (control group) received only distilled water. Rats in groups 2 and 3 were sacrificed after the collection of blood and tissue samples on the 28th and 56th days, respectively. We found significant differences in bilirubin, alkaline phosphatase, lactate dehydrogenase, glucose, triglyceride, very-low-density lipoprotein, and iron values (p < 0.050 for all) but none in any other parameter (p > 0.050). All rats in the control group had normal histological features; however, none of the rats in groups 2 and 3 showed normal histology. In group 2, we observed mild sinusoidal dilatation, congestion, enlarged Kupffer cells, accumulation of yellow-brown-black pigment in the Kupffer cells and the accumulation of hemosiderin with Prussian blue reaction in the hepatocytes. In group 3, the findings mentioned above were more prominent, and besides these findings focal acinar transformation and macrovesicular steatosis were also observed. In group 3, mild inflammation within the portal areas was observed consisting of lymphocytes, neutrophils, and eosinophils. This study is the first that reports the biochemical and histopathological evaluation of pazopanib-related hepatic toxicity.

Assessment of Multi Fragment Melting Analysis System (MFMAS) for the Identification of Food-Borne Yeasts.

Multi Fragment Melting Analysis System (MFMAS) is a novel approach that was developed for the species-level identification of microorganisms. It is a software-assisted system that performs concurrent melting analysis of 8 different DNA fragments to obtain a fingerprint of each strain analyzed. The identification is performed according to the comparison of these fingerprints with the fingerprints of known yeast species recorded in a database to obtain the best possible match. In this study, applicability of the yeast version of the MFMAS (MFMAS-yeast) was evaluated for the identification of food-associated yeast species. For this purpose, in this study, a total of 145 yeast strains originated from foods and beverages and 19 standard yeast strains were tested. The DNAs isolated from these yeast strains were analyzed by the MFMAS, and their species were successfully identified with a similarity rate of 95% or higher. It was shown that the strains belonged to 43 different yeast species that are widely found in the foods. A clear discrimination was also observed in the phylogenetically related species. In conclusion, it might be suggested that the MFMAS-yeast seems to be a highly promising approach for a rapid, accurate, and one-step identification of the yeasts isolated from food products and/or their processing environments.

Carbonic anhydrase IX is a prognostic biomarker in glioblastoma multiforme.

The identification of prognostic factors in patients with glioblastoma multiforme (GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA-IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA-IX in GBM remains largely unknown. In the present study, we evaluated the prognostic role of CA-IX in GBM patients. In total, 66 consecutive patients with GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all patients received temozolomide chemotherapy for at least 3 months. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on survival. The median OS was longer in patients with low levels of CA-IX expression (18 months) compared to patients overexpressing CA-IX (9 months) (P = 0.004). There was not a statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054) between patients with high or low levels of CA-IX expression. In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio (HR), 3.703; P = 0.001), CA-IX overexpression (HR, 1.967; P = 0.019), and incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross-total resection (HR, 1.956; P = 0.034). Our findings indicated that CA-IX may be a potential prognostic biomarker in the treatment of GBM.

Structure and function of the PP2A-shugoshin interaction.

Accurate chromosome segregation during mitosis and meiosis depends on shugoshin proteins that prevent precocious dissociation of cohesin from centromeres. Shugoshins associate with PP2A, which is thought to dephosphorylate cohesin and thereby prevent cleavage by separase during meiosis I. A crystal structure of a complex between a fragment of human Sgo1 and an AB'C PP2A holoenzyme reveals that Sgo1 forms a homodimeric parallel coiled coil that docks simultaneously onto PP2A's C and B' subunits. Sgo1 homodimerization is a prerequisite for PP2A binding. While hSgo1 interacts only with the AB'C holoenzymes, its relative, Sgo2, interacts with all PP2A forms and may thus lead to dephosphorylation of distinct substrates. Mutant shugoshin proteins defective in the binding of PP2A cannot protect centromeric cohesin from separase during meiosis I or support the spindle assembly checkpoint in yeast. Finally, we provide evidence that PP2A's recruitment to chromosomes may be sufficient to protect cohesin from separase in mammalian oocytes.

Factors Influencing Chemotherapy Goal Perception in Newly Diagnosed Cancer Patients.

Cancer patients who start receiving chemotherapy have difficulty in understanding the state of their disease, the prognosis, and the purpose of treatment. We used a survey to evaluate the extent of perception of chemotherapy goal among cancer patients. Two hundred sixteen cancer patients who received chemotherapy for the first time participated in the study. The presence of depression and anxiety was assessed using the "Hospital Anxiety and Depression Scale" (HAD). The consistency between the patients' perception of the chemotherapy goal and the physician's perception was described as "right," and the inconsistency was described as "wrong." Among the patients who participated in the survey, 53.2 % (n = 115) were receiving adjuvant treatment and 46.8 % (n = 101) were receiving palliative treatment for metastatic disease. The rate of right and wrong perception of the chemotherapy goal was 51.9 % (n = 108) and 32.2 % (n = 67), respectively, and the rate of confused patients was 18.9 % (n = 41). The level of education was shown to be the only parameter involved in accurate perception of the treatment purpose (hazard ratio (HR) = 0.444, p = 0.025, 95 % confidence interval (CI) 0.219-0.903). In this study, there was a 51.9 % consistency between the physician's perception and that of the patient regarding the purpose of treatment. We demonstrated that the level of education was the unique factor in accurate perception of chemotherapy goal among cancer patients.

The impact of immunohistochemical staining with ezrin-carbonic anhydrase IX and neuropilin-2 on prognosis in patients with metastatic renal cell cancer receiving tyrosine kinase inhibitors.

The identification of prognostic factors in patients with renal cell carcinoma (RCC) represents an area of increasing interest. In this retrospective study, we evaluated the prognostic role of carbonic anhydrase-IX, ezrin, and neuropilin in metastatic RCC patients. The expression of several biomarkers were measured by immunohistochemistry (IHC) in 45 patients with advanced stage RCC treated with second-line tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) after failure of interferon-alpha between January 2007 and June 2012. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on the survival. Age, ezrin and neuropilin-2 overexpression were found to be statistically significant factors (P < 0.05) for PFS in the univariate analysis. Ezrin and neuropilin-2 overexpression, hemoglobin and albumin level were statistically significant factors (P < 0.05) for OS in the univariate analysis. Multivariate analysis revealed that low expression of ezrin and neuropilin-2 was an independent prognostic factor for PFS and OS. The median PFS was 4 months for patients overexpressing neuropilin-2 versus 11 months for those with lower expression of neuropilin-2 (p = 0.033). The median OS was longer in patients with low levels of neuropilin-2 expression (26 months) compared to patients overexpressing neuropilin-2 (13 months) (p = 0.023). Increased expression of ezrin was associated with poor prognosis in patients treated with TKIs targeting VEGF (PFS, 3 vs 7 months; p = 0.012). High ezrin expression was associated with shorter OS (p = 0.009). This is the first study in the literature showing that neuropilin-2 and ezrin are related with prognosis in patients with advanced RCC.