The knockdown of stathmin with si-RNA inhibits invasion of mesothelioma.

BACKGROUND: To investigate the mechanism of action of stathmin1 (STMN1) in mesothelioma (MSM) and whether it has any role in its treatment. METHODS: STMN1 expression was examined using immunohistochemistry in biopsy tissues taken from MSM patients. The relationships between the levels of STMN1 expression in the pathology preparations of MSM patients, and the clinicopathological characteristics of these patients, and their survival times were investigated. Transfection of STMN1-specific siRNA into SPC212 cells was compared to negative control siRNAs. The mRNA levels of genes that may play a role in invasion, apoptosis, and autophagy were evaluated by RT-PCR. RESULTS: The expression of STMN1 was shown to be high in MSM tissues (p < 0.05). It was found that the only independent predictor factor affecting the survival time of MSM patients was the disease stage (p < 0.05). STMN1 was significantly reduced after siRNA intervention (81.5%). STMN1 with specific siRNA has been shown to suppress invasion by reducing the mRNA levels of cadherin-6 (CDH6), fibroblast growth factor-8 (FGF8), hypoxia-inducible factor 1 (HIF1A), matrix metallopeptidase 1-2 (gelatinase A) (MMP1-2), and TIMP metallopeptidase inhibitor 2 (TIMP2), which are important markers for invasion. Although the expression of apoptosis and autophagy-related genes, caspase-2 (Casp2) and LC-3, was reduced by silencing STMN1 with specific siRNA in western blot analysis, this effect was not observed in PCR results. CONCLUSIONS: Immunohistochemical analysis of STMN1 may contribute to the differential diagnosis of MSM, and STMN1 may also be considered as a potential therapeutic target in the early invasive stage of MSM therapy.

Prognostic value of indoleamine 2, 3-dioxygenase-1 expression in glial tumors.

Background and purpose:

Gliomas are the most common primary malignant central nervous system tumors in adults, exhibiting a poor prognosis. Indoleamine 2, 3-dioxygenase-1 (IDO-1) has important functions in cancer immunotherapy due to its role in escaping cancer cells from the immune system. In this study we purposed to evaluate the correlation between IDO-1 expression and clinicopathological parameters in gliomas, and whether IDO-1 can be a prognostic marker.

n=75 patients in total, n=25 patients with low grade glial tumors (LGG, grade 1-2), n=25 patients with high grade glial tumors (HGG, grade 3-4), and n=25 persons with normal brain tissue as control group were included in this study. IDO-1 expression was categorized by using immunohistochemical staining in biopsy specimens as high (H) and low (L) groups among the patients with gliomas. We used a 95% percent confidence interval and p <0.05 to analyze the association between the degree of IDO-1 expression, clinicopathological characteristics, and survival rates in glioma patients. 

In HGG, IDO-1 levels were higher than in control brain tissue and LGG (p< 0.001). The mean overall survival (OS) was longer in the L-IDO-1 group (64.53 ± 3.34) in months (95% CI: 57.969-71.098) compared to the H-IDO-1 group (43.74 ± 4.36) in months, (95% CI: 35.218-52.330) (p< 0.05).

IDO-1 expression is an in­de­pendent prognostic biomarker to predict 
OS and progression in HGG. IDO-1 can be evaluated as an alternative instrument for precision medicine in the treatment of gliomas.

Fibulin1 and mesothelin expressions in pancreas ductal adenocarcinoma.

OBJECTIVE: The balance between malignant tumor cells and the connective tissue surrounding them determines the aggressiveness of the tumor. We aimed to understand the effects of mesothelin (MSLN) and fibulin1 (FBLN1) expressions on survival in pancreas ductal adenocarcinoma (PDCA), and also whether these proteins have prognostic value for PDCA. METHODS: Of 80 patients in total, 40 who underwent the Whipple procedure for diagnosed PDCA between 2009 and 2016, and 40 patients with diagnosed pancreatitis as the control group, were included in the present study. Immunohistochemically, MSLN, and FBLN1 expressions were evaluated retrospectively. We assessed the relationship between the degree of MSLN, FBLN1 expression, clinical-pathological features, and survival rates in PDCA cases. RESULTS: The median follow-up duration was 11.4 (3-41) months. All of the patients for MSLN and FBLN1 were immune reactive. We detected a significant difference in MSLN expression between patients with PDCA and control groups, but not in FBLN1 expression. MSLN, FBLN1 expressions were categorized as lower-higher (L/H) groupings. There was no difference in the median overall survival (OS) of patients in the MSLN groups. The L-FBLN1 group had a median OS of 18 months (95% CI: 9.51-26.48) versus 14 months (95% CI: 13.021-14.97) in the H-FBLN1 group (interconnective tissue) (p=0.035). According to Kaplan-Meier analysis, L-FBLN1 expression in the tumor microenvironment was associated with longer survival in PDCA. The FBLN1 expression in the tumor microenvironment was shown to be significantly inversely related to OS (p=0.05). CONCLUSION: The FBLN1 expression, which is in the tumor microenvironment of PDCA, may serve as a prognostic biomarker.

Reversible Severe Parkinsonism Caused by Extra-Pontine Myelinolysis in a patient with Primary Adrenal Failure.

PURPOSE: Extrapontine myelinolysis (EPM) is a highly uncommon, life-threatening disease, particularly in individuals who initially appear with severe clinical symptoms. Here, we describe a case of EPM caused by the rapid correction of hyponatremia that had severe clinical signs at first but parkinsonism symptoms were fully improved after treatment. CASE REPORT: A 46-year-old female patient was admitted to the hospital due to impaired consciousness. Her medical history reveals that she has PAI, or primary adrenal insufficiency. Initial laboratory measurements showed that the serum's sodium (Na) concentration was 104 mEq/L, chloride (Cl) content was 70 mmol/L, potassium (K) content was 4.95 mEq/L, glucose was 42 mg/dL, hydrogen potential (Ph) was 7.12, and bicarbonate (HCO3) concentration was 10 mmol/l. The adrenocorticotropic hormone (ACTH) level was 21 mg/ml, while the cortisol level was 1.2ug/dl. Her mental state was unclear, she had sluggish hypophonic speech, generalized akinesia/rigidity in both upper and lower extremities, trouble swallowing solid and liquid meals, and sialorrhea were all discovered after the Na level was corrected. Hyperintense lesions were visible in the bilateral putamen and caudate nuclei of the Magnetic Resonance Imaging (MRI) T2 and flair-weighted scans, which indicate EPM. EPM was treated with corticosteroids and dopamine agonists, and she was eventually released after complete recovery. CONCLUSION: Even if there are severe clinical symptoms at first, prompt diagnosis and treatment, such as dopaminergic, corticosteroid, and palliative therapy, can save a patient's life.

The Effects of Self-Acupressure on Pain, Fatigue, and Sleep Quality in Colon and Pancreatic Cancer Patients Receiving Chemotherapy: A Randomized Controlled Study.

BACKGROUND: Pancreatic and colon cancer are among important gastrointestinal cancer diseases. Pain, fatigue, and insomnia are among the most common symptoms in cancer patients receiving chemotherapy. Self-acupressure may improve patients' pain, fatigue, sleep quality, quality of life, and functional well-being. OBJECTIVE: The aim of this study was to examine the effects of self-acupressure application on pain, fatigue, and sleep quality in colon and pancreatic cancer patients receiving chemotherapy. METHODS: This randomized controlled study was conducted with 60 patients in treatment for pancreatic or colon cancer, 30 in the intervention and 30 in the control group, between June and October 2021. Participants in the intervention group were asked to complete 16 acupressure sessions for 4 weeks, 2 days a week in the morning and afternoon for a total of 18 minutes, depending on the preparation and pressure time on 4 pressure points. Control group participants did not receive any interventions during the study. The data were collected by using a personal information form, the Pittsburgh Sleep Quality Index, the Piper Fatigue Scale, and the visual analog scale. RESULTS: After self-acupressure, the visual analog scale, Piper Fatigue Scale, and Pittsburgh Sleep Quality Index scores of the intervention group decreased when compared with the control group scores; the difference between the 2 groups was statistically significant. CONCLUSION: Self-acupressure was effective in reducing the pain, fatigue, and sleep disorder scores of patients with colon or pancreatic cancer receiving chemotherapy. IMPLICATIONS FOR PRACTICE: In nursing practice, self-acupressure, an applicable, accessible, and inexpensive method in the management of cancer-related symptoms, can be supported and maintained during a 4-week period.

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.

Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study.

OBJECTIVES: To compare the survival of first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as first line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study. RESULTS: EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p = 0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p = 0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically significant (p = 0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically different than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p = 0.323). CONCLUSION: In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both first- and second-generation EGFR-TKIs should be considered, especially as first- and second-line options.

The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study).

INTRODUCTION: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI. MATERIALS AND METHODS: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ≥ 40% and low-positive group < 40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells. RESULTS: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n = 78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n = 113), but it was 10.8 months in the low-positive group (n = 98) (HR 0.39; 95% CI 0.25-0.60, p < 0.001). The median OS in the high-positive group was not reached, whereas it was 22.8 months in the low-positive group (HR 0.37; 95% CI 0.22-0.63, p < 0.001). ORR was significantly higher in the high-positive group (87.2 vs. 68.5%; p = 0.002). According to the cut-off values of < 20%, 20-39%, 40-59%, and ≥ 60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ≥ 60% group. CONCLUSION: Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs.

The overexpression of cyclin D1 is a positive prognostic factor in advanced-stage breast carcinoma cases.

OBJECTIVE: Cyclin D1 (CDDN1) is a protein required for mitotic cell cycle progression through the G1 phase, as well as a regulatory component of the cyclin-dependent kinases CDK4 and CDK6. In this study, we wanted to evaluate the relationship between CDDN1 expression and clinicopathological features in breast cancer (BC) cases and whether CDDN1 could be used as a prognostic biomarker for BC cases. METHODS: A total of 70 cases, 30 cases each with limited and advanced-stage BC, and as the control group, 10 healthy breast tissue, without a cancer diagnosis, with examined for benign reasons (mammoplasty, breast reduction surgery, etc.) were included in this study. The pathological specimens from the cases were stained, immunohistochemically, and categorized as a "low" (L) group or a "high" (H) group for CDDN1 expression. The cases' clinicopathological features and survival rates were evaluated statistically, within a 95% of confidence interval, p<0.05, retrospectively. RESULTS: The median follow-up period of the cases was 48.00 (range, 6-150) months. CDDN1 expression was significantly higher in advanced-stage BC cases than in normal breast tissue and limited-stage BC cases. The median overall survival (OS) was 96 months (CI 95%: 67.74-117.59) in the H-CDDN1 group, compared to the L-CDDN1 group not reached, but there was no relation (p>0.05). CDDN1 overexpression was more prominent in low-grade advanced BC cases (p=0.004). The median OS of advanced-stage BC cases with Grade 1 was significantly longer than those with other grades (p=0.04). CONCLUSION: Our results suggest that CDDN1 expression can be used as a potentially appropriate positive prognostic biomarker for advanced-stage BC cases.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).

Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.

siRNA-mediated stathmin1 silencing inhibits proliferation of prostate carcinoma cell line.

Stathmin1 (STMN1) has been proposed as a possible prognostic marker and a potential therapeutic target for some cancers. We aimed to analyze the changes in autophagy, invasion, apoptosis-related genes in prostate cancer (PCa) cell line (PC-3), after small interfering RNA (siRNA)-mediated STMN1 silencing, and also the relationships of STMN1 expression, clinicopathological parameters, and survival (OS) in PCa cases. The STMN1 expressions were analyzed, immunohistochemically, in formalin-fixed paraffin-embedded 75 PCa and 15 benign prostatic hypertrophy (BPH) tissues. The correlation between the levels of expression STMN1, clinicopathological features, and OS was determined in PCa cases. The siRNA-mediated STMN1 incubated PC-3 cells were transfected and compared to negative control siRNAs. We determined mRNA levels in autophagy, invasion, and apoptosis genes with the combination of reverse transcription-polymerase chain reaction (RT-PCR) and western blotting in PC3 cell lines after STMN1 silencing. It was determined that STMN1 was overexpressed significantly in PCa cases, immunohistochemically. The overexpression of STMN1 was significantly correlated with the high-grade Gleason score, and it was associated with a worse prognosis of PCa cases according to the Kaplan-Meier survival analysis (p < 0.05). Significant silencing in STMN1 was determined (87.5%) after siRNA applications. Especially, invasion genes such as claudin 7, fibroblast growth factor 8, hypoxia-inducible factor 1 subunit alpha, hepatocyte growth factor, matrix metallopeptidase 2, 7 genes, markedly, decreased by siRNA-mediated STMN1silencing. STMN1 silencing was determined to significantly increase caspase 3 protein expression by using western blot analysis (p < 0.001). Although STMN1 silencing did not have a significant effect on the induction of apoptosis and autophagy-related genes in PCa cells, it was shown to affect apoptotic mechanisms through the caps3 protein. siRNA-mediated STMN1 silencing decreases proliferation in the PCa cell line. It is thought that STMN1 can serve as a potential therapeutic target in the advanced stage-PCa, especially.

Investigation of the relationship between lymphocyte subsets and intestinal parasites.

We analyzed the peripheral blood lymphocyte subsets of cancer patients infected with intestinal parasites, with an aim to find out the relationship between the levels of different types of lymphocytes with the prognosis of patients. 201 cancer patients aged 18 and over were included. Stool samples of the patients were examined using native-lugol, trichrome, modified trichrome (Weber's Trichrome stain), and modified Ziehl-Neelsen staining methods. Microsporidia and Cryptosporidium parvum were investigated at the genus and species levels using PCR. Lymphocyte subsets were determined by flow cytometry in blood samples. One or more parasite species were detected in 115 (56.7%) patients. The most common parasite species were Microsporidia, Blastocystis and Entamoeba coli, respectively. The frequency of parasites was high in patients with low lymphocyte percentage, CD3+ T cell and CD3+ CD4+ T (Th) cell levels in blood samples studied by flow cytometry. Microsporidia infection was significantly higher in patients with low lymphocyte percentage and Th cell levels. Similarly, C. parvum infection was found to be significantly higher in patients with low T lymphocyte percentage and Th cell level. Finally, Blastocystis infection was significantly higher in patients with low lymphocyte percentage and CD4/CD8 ratio higher than 1. The decrease in lymphocyte percentage, CD3+ T cell and Th cell count, and low CD4/CD8 ratio in cancer patients increase the frequency of intestinal parasitic infections. Based on these results, lymphocyte subsets may help identify cancer patients at high risk of opportunistic parasites. We suggest that opportunistic parasitic infections affecting the clinical course of the disease should be considered by clinicians during the follow-up and treatment of patients.

Effect of Asbestos Exposure on the Frequency of EGFR Mutations and ALK/ROS1 Rearrangements in Patients With Lung Adenocarcinoma: A Multicentric Study.

OBJECTIVE: The aim of this study is to investigate the effect of asbestos exposure on cancer-driver mutations. METHODS: Between January 2014 and September 2018, epidermal growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK), and c-ros oncogene 1 receptor tyrosine kinase gene (ROS1) alterations, demographic characteristics, asbestos exposure, and asbestos-related radiological findings of 1904 patients with lung adenocarcinoma were recorded. RESULTS: The frequencies of EGFR mutations, ALK, and ROS1 rearrangements were 14.5%, 3.7%, and 0.9%, respectively. The rates of EGFR mutations and ALK rearrangements were more frequent in asbestos exposed non-smokers (48.7% and 9%, respectively). EGFR mutation rate was correlated to female gender and not-smoking, ALK rearrangement rate was correlated to younger age, not-smoking, and a history of asbestos exposure. CONCLUSIONS: The higher rate of ALK rearrangements in asbestos-exposed lung adenocarcinoma cases shows that asbestos exposure may most likely cause genetic alterations that drive pulmonary adenocarcinogenesis.

Investigation of Isolated Blastocystis Subtypes from Cancer Patients in Turkey.

PURPOSE: It is not clear that Blastocystis remains without damage to the digestive tract or has a pathogenic effect in relation to subtypes in immunocompromised people, such as cancer patients. The present study aimed to investigate the frequency and subtype distribution of Blastocystis in cancer patients who were followed-up and treated in the Oncology clinic of Firat University Hospital and to determine the clinical signs of infected sufferers. METHODS: 201 patients aged ≥ 18 with a diagnosis of cancer were enrolled in this cross-sectional study. Patients' stool samples were examined between September 2017 and August 2019 by native-Lugol, trichrome staining. Microscopy-positive stool samples were subjected to DNA isolation and subtyped by Sequence Tagged Site (STS)-PCR analysis. The symptoms and demographic characteristics of the patients were also evaluated. RESULTS: Totally, 29 (14.4%) samples were positive for Blastocystis after all methods. 15 (51.7%) out of 29 samples were successfully subtyped by the sequenced-tagged site(STS)-PCR, while 14 (48.3%) could not be typed. Three subtypes of Blastocystis were detected: ST3 (40%), ST2 (33%), ST1 (20%), and one mixed infections with ST1/ST2 (6%). There was no statistically significant difference in terms of clinical findings and demographic characteristics. CONCLUSION: The outcomes of our study promote the idea that Blastocystis could be an asymptomatic and harmless commensal organism. However, more comprehensive molecular and clinical studies are needed to fully determine the pathogenicity and epidemiology of Blastocystis in cancer patients.

Treatment approaches for managing patients with hematological malignancies in the time of COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is a unique challenge to the care of patients with hematological malignancies. We aim to provide supportive guidance to clinicians making individual patients decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. DISCUSSION: This review also provides recommendations, which are convenient in evaluating indications for therapy, reducing therapy-associated immunosuppression, and reducing healthcare utilization in patients with specific hematological malignancies in the COVID-19 era. Specific decisions regarding treatment of hematological malignancies will need to be individualized, based on disease risk, risk of immunosuppression, rates of community transmission of SARS-CoV-2, and available local healthcare resources.

A preliminary study: is fibulin 1 a friend or an enemy that needs to be silenced with siRNAs for mesothelioma?

INTRODUCTION: The impaired balance between cell proliferation and cell death, followed the inability to receive the death signals, cells push towards the neoplasia pathway. Fibulin 1 (FBLN1) plays a role as a co-factor in the mechanism of action of a protease such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-1), which has important roles in angiogenesis, can also act as both tumor suppressor gene (TSG) and an oncogene in the main constituent of the extra-cellular matrix. This preliminary study has investigated the effects of silencing FBLN1 with siRNA on autophagy, proliferation, apoptosis pathways in the MSM cell line. MATERIAL AND METHODS: It was transfected siRNA specific to FBLN1 incubated MSM SPC212 cells, and compared with negative control siRNAs by a real-time polymerase chain reaction. It was determined apoptosis, proliferation, autophagy-related genes in mRNA levels. RESULTS: It was observed that increased anti-apoptosis genes, such as CASP2, CASP7, DDFA, and BCL2, anti-apoptotic gene, reduced APAF1, CASP8. Proliferation induced through while increased ADAMTS1, CDH1, CDH6, CLDN7, CSF3, MMP7, MMP13 genes. Autophagy increased via increasing MAP1LC3B, ATG-16L1 genes while decreased via suppressed ULK1, and ATG7 genes by silencing FBLN1 with siRNAs (p < 0.05). CONCLUSIONS: Proliferation can be induction with silencing of FBLN1 with siRNA in processing mechanism MSM. It was concluded that FBLN1 could be act as pleiotropic on autophagy, and apoptosis pathways in proliferation processing for MSM. Therefore we think that FBLN1 acts like a TSG. FBLN1 can be considered as a targeted treatment option in advanced stage MSM.

Clinicopathologic and Prognostic Differences between Three Different Age Groups (Child/Adolescent, Young Adults, and Adults) of Colorectal Cancer Patients: A Multicentre Study.

BACKGROUND: Colorectal cancer (CRC) is a rare disease amongst children and adolescents. Previous studies have reported a number of differences between children/adolescents, young adults, and adult patients with CRC. However, none of these studies compared these age groups according to their clinicopathologic and prognostic characteristics. In the current study, we compare these three age groups. METHODS: A total of 173 (1.1% of 15,654 patients) young CRC patients (≤25 years) were included in the study. As a control group, 237 adult CRC patients (>25 years) were also included. Patients were divided into three age groups: child/adolescent (10-19 years), young adult (20-25 years), and adult (>25 years). RESULTS: Statistical differences amongst the three groups in terms of gender (p = 0.446), family history (p = 0.578), symptoms of presentation (p = 0.306), and interval between initiation of symptoms and diagnosis (p = 0.710) could not be demonstrated. Whilst abdominal pain (p < 0.001) and vomiting (p = 0.002) were less common in young adults than in other groups, rectal bleeding and changes in bowel habits were relatively less common in adolescents than in other groups. Rectal localisation (p = 0.035), mucinous adenocarcinoma (p < 0.001), and a poorly differentiated histologic subtype (p < 0.001) were less common in the adult group than in other groups. The percentage of patients with metastasis and sites of metastasis (e.g., peritoneum and lung) differed between groups. The median overall survival was 32.6 months in the adolescent group, 57.8 months in the young adult group and was not reached in the adult group (p = 0.022). The median event-free survival of the adolescent, young adult, and adult groups was 29.0, 29.9, and 61.6 months, respectively (p = 0.003). CONCLUSIONS: CRC patients of different age groups present different clinicopathologic and prognostic characteristics. Clinicians should be aware of and manage the disease according to these differences.