Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wild-type patients treated with biologics second-line mCRC.

BACKGROUNDS AND OBJECTIVES: Colorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311). MATERIALS AND METHODS: In this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups. RESULTS: A total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848). CONCLUSION: According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

Efficacy of 5-aminolevulinic acid-based photodynamic therapy in different subtypes of canine mammary gland cancer cells.

Canine mammary gland tumors (CMGTs) are heterogeneous disease and subclassified [sarcomas (S), carcinomas (C), and carcinosarcomas (CS)] according to histopathological differentiation. Photodynamic therapy (PDT) is a promising treatment strategy based on the use of a photosensitizer (PS) activated by light. However, the therapeutic potential of PDT in the treatment of CMGTs has not been investigated, yet. Therefore, the aim of this study was to determine the in vitro protocol of 5-ALA-based-PDT for the treatment of three subtypes of CMGTs, for the first time. The intracellular PpIX florescence intensity was measured for 5-ALA (0.5 and 1 mM). After irradiation with different light doses (6, 9, 12, 18, and 24 J/cm2) for two different modes [continuous wave (CW) and pulse radiation (PR)], the cytotoxic effects of 5-ALA (0.5 and 1 mM) on the subtypes (C, S, and CS) of CMGTs were analyzed by WST-1. Finally, the optimal PDT treatment protocol was validated through Annexin V and AO/EtBr staining. Our results showed that 1 mM 5-ALA for 4-h incubation was the best treatment condition in all subtypes of CMGTs due to higher intracellular PpIX level. After irradiation with different light doses, PR mode was more effective in S primary cells at 9 J/cm2. However, a significant decrease in the viability of C and CS cells was detected at 12 /cm2 in CW mode (p < 0.05). Additionally, 1 mM 5-ALA induced apoptotic cell death in each subtype of CMGTs. Our preliminary findings suggest that (i) each subtype of CMGTs differentially responds to PDT and (ii) the light dose and mode could play an important role in the effective PDT treatment. However, further studies are needed to investigate the role of the different light sources and PDT-based apoptotic cell death in CMGTs cells.

The efficacy of indoximod upon stimulation with pro-inflammatory cytokines in triple-negative breast cancer cells.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) inhibition has received much attention in cancer immunotherapy due to its role in immune escape in cancer cells. Additionally, changes in the pro-inflammatory cytokine levels can affect tumor growth and metastasis as well as the effectiveness of immunotherapy. The purpose of this study was for the first time to determine the effects of indoximod as an IDO inhibitor on triple-negative breast cancer (TNBC) and to assess the link between the efficacy of indoximod and IFN-γ or TNF-α stimulation. METHODS: The cytotoxic and apoptotic effects of indoximod alone or IFN-γ or TNF-α induction to mimic an inflammatory environment were evaluated by WST-1, Annexin V, cell cycle analysis, and acridine orange (AO)/ethidium bromide (EtBr) staining. Furthermore, the expression levels of IDO1 and PD-L1 expression were analyzed by RT-PCR. RESULTS: Our results demonstrated that indoximod significantly decreased the TNBC cell viability through apoptotic cell death (p < .05). The combination of indoximod and TNF-α was more effective than indoximod and IFN-γ stimulation or indoximod alone in TNBC cells. Additionally, PD-L1 expression level was significantly up-regulated after treatment with indoximod and TNF-α or IFN-γ combinations (p < .05). CONCLUSIONS: Indoximod exhibited a therapeutic potential in TNBC cells and pro-inflammatory cytokines could affect the effectiveness of indoximod. However, further studies are required to identify the role of the IDO-associated signaling pathways, the molecular mechanisms of indoximod induced apoptotic cell death, and the relationship between IDO inhibition by IDO inhibitors and pro-inflammatory cytokine levels.

Some, but not all of the premenstrual syndrome symptoms affect the medical exam scores in medical students.

OBJECTIVES: This research aims to identify the effects of premenstrual syndrome (PMS) symptoms on the school exam scores in medical students. METHODS: This cross-sectional study was designed at Sakarya University School of Medicine The study included medical students who were in the first, second, and third year of class. In this study, there were 193 male and 100 female students. The study investigated how PMS symptoms affected medical student's exam scores and school success. All exam scores were recorded during the two-consecutive semester so duration of study was one year. RESULTS: There were 100 female students, and they had five different committee exams for one year. Female student's exam scores were significantly higher for four committees and an average score of all year. The mean age of female students was 19.9 ±1.5. Acne, nausea/vomiting, sleeping, abdominal bloating, and prurience change had significantly different exam scores compared to the group without these symptoms. Students with acne had substantially higher exam scores than without acne; inversely, the other four symptoms negatively affected exam scores. CONCLUSION: Some of the PMS symptoms can be more annoying and should change the quality of life more than the other symptoms, so we should define these symptoms to improve our student's quality of life and school success.

Synergistic Effects of Nobiletin and Sorafenib Combination on Metastatic Prostate Cancer Cells.

Objective: Herein we, for the first time, investigated a potential synergistic effect of nobiletin (NOB) and sorafenib (SOR) on PC-3 prostate cancer and HUVEC control cell lines. Methods: In order to determine the cytotoxic and apoptotic effects of the combination of NOB and SOR, WST-1, Annexin V, and cell cycle analysis were performed. The potential molecular mechanism of apoptotic cell death was assessed by Bax, Bcl-2, CCDN1, Rb1, and CDKN1A gene expression and acridine orange (AO) and DAPI staining. Results: Our results indicated that NOB and SOR combination had a significant inhibitory effect on the viability of PC-3 cells with less toxicity on HUVEC cells than SOR alone (P < 0.01). NOB and SOR combination significantly caused much more apoptotic cell death and cell cycle arrest at G0/G1 phase by up-regulation of Bax, Rb1, and CDKN1A levels in PC-3 cells (P < 0.01). Therefore, strong synergistic effects between NOB and SOR were analyzed (CI < 1). Conclusion: NOB and SOR combination was more effective than SOR and NOB alone and reduced the exposure time for SOR and NOB in PC-3 cells. Combination strategy is a therapeutic potential to improve efficacy and reduce side-effect of SOR for the treatment of metastatic prostate cancer cells.

Inhibition of TLR4/TRIF/IRF3 Signaling Pathway by Curcumin in Breast Cancer Cells.

PURPOSE: Toll-like receptor 4 (TLR4) is over-expressed in breast tumors and thus contributing to the tumor progression and metastasis. Natural products have drawn attention in cancer immunotherapy due to their various biological activities. Curcumin is well investigated in different types of cancer. However, the mechanisms underlying its anti-inflammatory actions have not been extensively elucidated.  For this purpose, we explored the inhibitory effects of curcumin on lipopolysaccharide (LPS)-induced TLR4 dependent TRIF signaling pathway in two subtypes of breast cancer cell lines (MCF-7 and MDA-MB-231) in this study. METHODS: In this context, the cytotoxicity of curcumin and LPS alone and the combination of curcumin with LPS on these cells was evaluated by WST-1 assay.  The expression level of TLR4 and the release of type I interferon (IFN) levels were determined after treatment with curcumin and/or LPS by RT-PCR and ELISA analysis, respectively. Furthermore, the subcellular localization of TLR4 and interferon regulatory factor 3 (IRF3) were detected by immunofluorescence analysis. RESULTS: Curcumin treatment suppressed breast cancer cells viabilities and the activation of TLR4-mediated TRIF signaling pathway by the downregulation of TLR4 and IRF3 expression levels and the inhibition of type I IFN (IFN-α/ß) levels induced by LPS. However, curcumin was more efficient in MDA- MB-231 cells than MCF-7 cells owing to its greater inhibitory efficacy in the LPS- enhanced TLR4 signaling pathway. Furthermore, IFN-α/ß levels induced by TLR4 and IRF3 were decreased in these cells following curcumin treatment. CONCLUSIONS: Consequently, these results demonstrated that the activation of LPS stimulated TLR4/TRIF/IRF3 signaling pathway was mediated by curcumin in breast cancer cells, in vitro. However, more studies are necessary to examine the curcumin's anti-inflammatory activities on TLR4/MyD88/NF-κB as well as other signaling pathways downstream of TLRs in breast cancer.

Is Change in Hemoglobin Level a Predictive Biomarker of Tyrosine Kinase Efficacy in Metastatic Renal Cell Carcinoma? A Turkish Oncology Group Study.

BACKGROUND: There are insufficient predictive markers for renal cell carcinoma (RCC). METHODS: A total of 308 metastatic RCC patients were analyzed retrospectively. RESULTS: The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.5 versus 6.35 months (p < .001) and 21.0 versus 11.36 months (p < .001) respectively. The 1- and 3-year OS rates were higher in the Hb increased group, i.e., 84% versus 64% and 52% versus 35% respectively. CONCLUSIONS: The present study showed that increased Hb levels after tyrosine kinase inhibitor therapy could be a predictive marker of RCC.

The effects of zoledronic acid on ECG: a prospective study on patients with bone metastatic cancer.

INTRODUCTION: There are controversial results in the risk of atrial fibrillation as well as arrhythmogenic potential of bis-phosphonates. METHOD: 37 patients and 40 healthy controls were evaluated prospectively with regard to the cardiac side effects related to the use of zoledronic acid (ZA) and its effects on electrocardiography (ECG) parameters. RESULT: As the basal ECG results of the patients diagnosed with cancer compared with the control group, it was determined that QT maximum was significantly lower, QT minimum was significantly higher. However; it was determined that QT disp, P max, P min, and P disp values were not significantly different. There was no statistically significant difference in P max, P min, P disp, QT max, QT min, QT disp values of the ECG parameters measured from cancer patients, before and 60 minutes after ZA therapy. CONCLUSION: There were no significant alterations in ECG in the acute period, indicated that ZA had no arrhythmia potential in the early period in patients with no underlying cardiac disease. However: patients receiving ZA should be monitored more closely because of the risk of arrhythmia which may ensue due to hypocalcemia, hypomagnesemia, or other chemotherapeutics.

Tendency of cancer patients and their relatives to use internet for health-related searches: Turkish Oncology Group (TOG) Study.

PURPOSE: This study aimed to reveal the habits of using internet by cancer patients and their relatives to access health-related information and services in Turkey. METHODS: An 18-item questionnaire survey was applied in cancer patients and their relatives. RESULTS: A total of 1106 patients (male, 37.3%, and female, 62.7%) and their relatives were included in the study. The responders had been using internet to obtain health information about oncological diseases, once a month (34.2%), 1-2 times a week (27.4%) or 2-3 times a month (21.9%). After diagnosis of cancer was made, participants more frequently (64.4%) investigated health-related issues, while 64.9% of them considered internet as an important search tool, and 16.7% of them had thought to give up cancer therapy under the influence of internet information. Some (33.1%) participants had used herbal medicine, and 16.7% of them had learnt these herbal products from internet. Still 12.7% of them had not questioned the accuracy of internet information, while 26.9% of them indicated that they had not shared the internet information about cancer with their physicians, and 13 % of them searched information in internet without asking their physicians. CONCLUSION: Cancer patients and their relatives showed a higher tendency to use health-related internet information which may mislead them, and can result in treatment incompliance. Health professionals should offer evidence-based information to the patients and their relatives through internet.

Evaluation of prognostic factors and treatment in advanced small bowel adenocarcinoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology (ASMO).

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Since these are rarely encountered tumors, there are limited numbers of studies investigating systemic treatment in advanced SBA. The purpose of this study was to evaluate the prognostic factors and systemic treatments in patients with advance SBA. METHODS: Seventy-one patients from 18 Centers with advanced SBA were included in the study. Fifty-six patients received one of the four different chemotherapy regimens as first-line therapy and 15 patients were treated with best supportive care (BSC). RESULTS: Of the 71 patients, 42 (59%) were male and 29 (41%) female with a median age of 56 years. Median follow- up duration was 14.3 months. The median progression free survival (PFS) and overall survival (OS) were 7 and 13 months, respectively (N=71). In patients treated with FOLFOX (N=18), FOLFIRI (N=11), cisplatin-5-fluorouracil/ 5-FU (N=17) and gemcitabine alone (N=10), median PFS was 7, 8, 8 and 5 months, respectively, while median OS was 15, 16, 15 and 11 months, respectively. No significant differences between chemotherapy groups were noticed in terms of PFS and OS. Univariate analysis revealed that chemotherapy administration, de novo metastatic disease, ECOG PS 0 and 1, and overall response to therapy were significantly related to improved outcome. Only overall response to treatment was found to be significantly prognostic in multivariate analysis (p=0.001). CONCLUSIONS: In this study, overall response to chemotherapy emerged as the single significant prognostic factor for advanced SBAs. Platin and irinotecan based regimens achieved similar survival outcomes in advanced SBA patients.

The influence of cisplatin, doxorubicin, pegylated doxorubicin, oxaliplatin and gemcitabine on mahlavu cell line.

PURPOSE: Hepatocellar carcinoma (HCC) remains a major health problem being the third leading cause of deaths due to cancer worldwide. Because HCC is known to be highly resistant to conventional systemic therapies, single-agent or combination of systemic therapies have been investigated. Today, sorafenib, a multikinase inhibitor, is the only approved systemic agent for the first line treatment of advanced HCC. In this study, we aimed to investigate the influence of different concentrations of cisplatin, doxorubicin, pegylated doxorubicin (PLD), oxaliplatin and gemcitabine by applying these agents either single or in combinations on mahlavu cell line. METHODS: HCC mahlavu cell line was used for the experiments. Cell death was measured by flow cytometry at 48 hrs after incubation with various concentrations (0.1 µg/ml, 1.0 µg/ml and 10 µg/ml) of the drugs. RESULTS: Cell death due to gemcitabine was found to be significantly higher than cell deaths caused by the other single agents including cisplatin, oxaliplatin, doxorubicin and PLD (p<0.001, p<0.001, p<0.001 and p=0.0049, respectively). There was no significant difference between gemcitabine and both the gemcitabine combination with doxorubicin and PLD (p=0.992 and p=0.441, respectively). CONCLUSION: This is a preliminary analysis evaluating the effect of the conventional chemotherapeutic agents on mahlavu cell line in vitro. The findings of this study suggest that gemcitabine-based therapies keep on being the prefered therapeutic approach for the treatment of HCC.

Increased serum procalcitonin levels in pregnant patients with asymptomatic bacteriuria.

BACKGROUND: Among the pregnancy urinary tract infections, asymptomatic bacteriuria (ASB) is the most common one. Untreated ASB can progress to pyelonephritis in 30-50% of the patients and can also result in prematurity in 27% of the pregnancy so it needs immediate diagnosis and treatment. In this study, we wanted to evaluate procalcitonin levels, compared to other inflammatory in pregnant women with ASB. METHODS: The study was designed between the period of January 2012 and February 2013 at Sakarya University School of Medicine, Department of Gynecology and Obstetrics. The study population included 30 pregnant patients with asymptomatic bacteriuria and 39 healthy pregnant controls. RESULTS: Mean age was 28 (SD, 5.5) of the study population; mean maternal weight was 70 (SD, 8) kilogram. There were no statically significant differences between the groups according to the routine biochemical parameters, but gestational age was significantly lower in the ASB group compared to the controls (20.4 vs 28.6, respectively; p < 0.001). Serum procalcitonin levels were negative in all of the controls. In ASB group, 9 (30%) patients had procalcitonin levels greater than >0.05 ng/ml and 21(70%) patients had negative procalcitonin levels (Chi-squrae, p < 0.001). The sensitivity and specificity of procalcitonin assay for ASB was calculated as 30% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 65%. The most frequent microorganisms in the urine culture were Escherichia coli (26 patients, 87%), Proteus mirabilis (3 patients, 10%) and Klebsiella (1 patient, 3%) in the ASB group. We experienced four (44%) recurrences among nine positive procalcitonin in ASB patients after completion of treatment of the first ASB diagnosis. DISCUSSION: Procalcitonin levels were significantly higher in ASB group than the control group and serum procalcitonin levels were higher in pregnant women with recurrent ASB. This finding is an important result revealed that high procalcitonin level can predict the further urinary tract infection risk. Finally, serum procalcitonin levels were normal in healthy pregnant women while other inflammatory markers such as WBC, ESR and CRP levels were higher.

MELD-sodium score and its prognostic value in malignancy-related ascites of pancreatic and gastric cancer.

BACKGROUND: Malignant ascites is a manifestation of end-stage events in a variety of cancers. There is significant lack of possible survival predictors in patients with malignancy-related ascites. Since the Model for End-Stage Liver Disease (MELD)-Na score has been shown to be a feasible and independent prognostic predictor for both short- and long-term outcome in HCC patients, we decided to test its prognostic role in other cancer types with ascites. MATERIAL AND METHODS: This is a retrospective study. The outpatient oncology clinic's records were screened for the period between 2004 and 2011. Eighty-two pancreatic and gastric cancer patients were enrolled into the study. RESULTS: The median age of patients was 59 (±12). Fifty-nine patients had gastric cancer and 23 had pancreatic cancer. Overall survival (OS) was 16.8 (IR, 1-98) months in gastric cancer and 16.3 (IR, 0.5-81) months in pancreatic cancer. There was no statistically significant difference between OS of gastric and pancreatic cancer. Progression-free survival (PFS) was statistically significantly longer in gastric cancer than pancreatic cancer with 16.5 (IR, 0.5-90) vs 6.5 (IR, 0.4-34) months (P = 0.04). Further analysis of data included stepwise multiple regression analysis with the dependent variable "overall survival." The model had two independent predictors and an R(2) of 82 % and a predicted R(2) of 81 %. Predictors for time to remission were PFS and MELD-Na. The regression equation for the model was: Overall survival =17.4- 0.522 MELD-Na + 0.902 PFS CONCLUSION: In this study we showed that progression-free survival and MELD-Na score are significantly related with overall survival. MELD-Na score can be one of the predictors of the survival and PFS in pancreatic and gastric cancer patients with ascites.

The cytotoxic effects of indoleamine 2, 3-dioxygenase inhibitors on triple negative breast cancer cells upon tumor necrosis factor α stimulation.

Context: Overexpressed indoleamine 2,3-dioxygenase (IDO) has been observed in many types of cancer and plays an essential role in the tumor microenvironment through immune cells function. Aims: In our study, the therapeutic potentials of two different IDO inhibitors (Epacadostat [EPA] and 1-methyl-L-tryptophan [L-1MT]) in triple-negative breast cancer (TNBC) cells were assessed with and without tumor necrosis factor-α (TNF-α) stimulation. Materials and Methods: The anticancer activity of EPA and L-1MT alone and in combination with TNF-α was analyzed by WST-1, annexin V, cell cycle analysis, and acridine orange/ethidium bromide staining. In addition, the relationship between IDO1 and programmed death-ligand 1 (PD-L1) expressions in TNBC cells upon treatment with IDO inhibitors was evaluated by reverse transcription-polymerase chain reaction analysis. Statistical Analysis Used: SPSS 22.0 was conducted for statistical analysis. The one-way analysis of variance with Tukey's multiple comparison test was performed for multiple groups. Independent (unpaired) t -test was used for the comparison of two groups. Results: EPA and L-1MT alone significantly suppressed the TNBC cell viability through the induction of apoptotic cell death and G0/G1 arrest (P < 0.05). TNF-α alone induced the overexpression of IDO1 and PD-L1 in TNBC cells compared with MCF-10A control cells. However, IDO inhibitors significantly inhibited overexpressed IDO1 mRNA levels. Furthermore, EPA alone and co-treated with TNF-α suppressed the mRNA level of PD-L1 in TNBC cells. Therefore, TNF-α stimulation enhanced the therapeutic effects of IDO inhibitors on TNBC. Conclusions: Our findings showed that the efficacy of IDO inhibitors was mediated by pro-inflammatory cytokine. However, different molecular signaling pathways are associated with pro-inflammatory cytokines production, and the expression of IDO1 and PD-L1 calls for further investigations.

Effect of the MiR-99b and MiR-135b on peritoneal carcinomatosis and liver metastasis in colorectal cancer.

AIM: This study aimed to evaluate the expression levels of miR-99b and miR-135b in peritoneal carcinoma and liver metastases associated with Colorectal Cancer (CRC), assess their association with the intracellular signaling pathway proteins Kirsten Rat Sarcoma Virus (KRAS) and Akt, and investigate their effects on survival. MATERIALS AND METHODS: Changes in the KRAS gene and Akt proteins, expression levels of miR-99b and miR-135b, and factors affecting survival were compared between colorectal cancer-associated peritoneal carcinomatosis and liver metastasis. RESULTS: The expression levels of miR-99b and miR-135b and the immunohistochemical grade classification score of Akt were higher in colorectal cancer, peritoneal carcinomatosis, and liver metastasis than in normal tissues (p < 0.05). MiR-99b expression was highest in CRC, whereas miR-135b expression was highest in peritoneal carcinomatosis (p < 0.05). The expression level of miR-99b decreased and that of miR-135b increased in peritoneal and liver metastases compared with that in the tumor tissue. MiR-99b, Akt, and recurrence were risk factors that affected the overall survival rate in the model of clinical predictions (p = 0.045, p = 0.006, and p = 0.012, respectively). CONCLUSION: While the expression of miR-99b was highest in the primary tumor, its decrease in liver metastasis and peritoneal carcinomatosis suggests that miR-99b has a protective effect against liver metastasis and peritoneal carcinomatosis. However, the detection of miR-135b expression was highest in peritoneal carcinomatosis and liver metastasis compared with that in the colorectal cancer tissues suggesting that it facilitates peritoneal carcinomatosis and liver metastasis. Furthermore, miR-99b, KRAS mutations, and Akt are risk factors for the overall survival of colorectal cancer.

The prognostic and predictive values of differential expression of exosomal receptor tyrosine kinases and associated with the PI3K/AKT/mTOR signaling in breast cancer patients undergoing neoadjuvant chemotherapy.

PURPOSE: Cancer cell-derived exosomes are the mediator of the tumor microenvironment and the molecular content of exosomes presents a promising prognostic or predictive marker in tumor progression and the treatment response of cancer patients. The aim of this study was to identify the expression levels of receptor tyrosine kinases (RTKs) and AKT1 and mTOR before and after neoadjuvant chemotherapy (NACT) in the exosomes of BC patients compared with healthy females. METHODS: After isolating exosomes in the serum of 25 BC patients and characterization by flow cytometry, the mRNA levels of FGFR2, FGFR3, PDGFRB, AKT1 and mTOR in the exosomes were analyzed by RT-PCR. RESULTS: Our preliminary findings showed that FGFR2, PDGFRB, AKT1 and mTOR levels were significantly upregulated in BC patients before NACT compared with the healthy group (p < 0.05). Furthermore, the mRNA levels PDGFRB and AKT1 were significantly down-regulated after NACT compared with control. PDGFRB expression level could predict pathological non-response and significantly correlated with tumor size after NACT. CONCLUSION: Therefore, especially FGFR2, PDGFRB and AKT1 could be a therapeutic target as a prognostic marker, whereas PDGFRB may be a promising predictive indicator of therapy response in BC patients. However, the prognostic or predictive role of RTKs and PI3K/AKT/mTOR signaling in the exosomes should be further investigated in a large patient population.

Prospective analysis of febrile neutropenia patients with bacteraemia: the results of an international ID-IRI study.

OBJECTIVES: Bacteraemia during the course of neutropenia is often fatal. We aimed to identify factors predicting mortality to have an insight into better clinical management. METHODS: The study has a prospective, observational design using pooled data from febrile neutropenia patients with bacteraemia in 41 centres in 16 countries. Polymicrobial bacteraemias were excluded. It was performed through the Infectious Diseases-International Research Initiative platform between 17 March 2021 and June 2021. Univariate analysis followed by a multivariate binary logistic regression model was used to determine independent predictors of 30-d in-hospital mortality (sensitivity, 81.2%; specificity, 65%). RESULTS: A total of 431 patients were enrolled, and 85 (19.7%) died. Haematological malignancies were detected in 361 (83.7%) patients. Escherichia coli (n = 117, 27.1%), Klebsiellae (n = 95, 22% %), Pseudomonadaceae (n = 63, 14.6%), Coagulase-negative Staphylococci (n = 57, 13.2%), Staphylococcus aureus (n = 30, 7%), and Enterococci (n = 21, 4.9%) were the common pathogens. Meropenem and piperacillin-tazobactam susceptibility, among the isolated pathogens, were only 66.1% and 53.6%, respectively. Pulse rate (odds ratio [OR], 1.018; 95% confidence interval [CI], 1.002-1.034), quick SOFA score (OR, 2.857; 95% CI, 2.120-3.851), inappropriate antimicrobial treatment (OR, 1.774; 95% CI, 1.011-3.851), Gram-negative bacteraemia (OR, 2.894; 95% CI, 1.437-5.825), bacteraemia of non-urinary origin (OR, 11.262; 95% CI, 1.368-92.720), and advancing age (OR, 1.017; 95% CI, 1.001-1.034) were independent predictors of mortality. Bacteraemia in our neutropenic patient population had distinctive characteristics. The severity of infection and the way to control it with appropriate antimicrobials, and local epidemiological data, came forward. CONCLUSIONS: Local antibiotic susceptibility profiles should be integrated into therapeutic recommendations, and infection control and prevention measures should be prioritised in this era of rapidly increasing antibiotic resistance.

Predicting the Overall Survival in Patients with Advanced Pancreatic Cancer by Calculating L3 Skeletal Muscle Index Derived from CT.

BACKGROUND: Pancreatic cancer is mostly diagnosed in advanced stages, and treatment results are not satisfactory. L3 skeletal muscle index (SMI) has emerged as a prognostic factor in pancreatic cancer patients. We aimed to assess the association between sarcopenia and overall survival in patients with pancreatic cancer in this study. METHODS: Patients who were admitted to the Department of Oncology between March 2012 and December 2019 and diagnosed with pancreatic cancer were evaluated. The computerized tomography images and laboratory parameters of a total of 115 patients were included in this retrospective singlecenter study. We defined sarcopenia as an SMI <43,56 cm²/m² for females and <56,44 cm²/m² for males using the receiver operating characteristics (ROC) curve in the study population. Univariate and multivariate analyses were performed by using Cox-regression modelling, and survival curves were constructed by using Kaplan-Meier method. RESULTS: 70% of the patients were male, and the mean age was 64.9±9.9 years (mean ± SD). 70.6% of female patients and 67.9% of male patients were diagnosed with stage 4 cancer. The prevalence of sarcopenia in the whole patient group was 29.6%. By multivariate analysis, SMI (p=0.009) and advanced stage (p=0.003) were found as poor prognostic factors for overall survival (OS). The neutrophil to lymphocyte ratio (NLR) was statistically significantly higher in sarcopenic patients than in nonsarcopenic patients (p=0.031). CONCLUSION: Patients having sarcopenia at the time of diagnosis may demonstrate poorer overall survival of pancreatic cancer, and SMI may be considered as a potential prognostic factor.