Isocoumarins incorporating chalcone moieties act as isoform selective tumor-associated carbonic anhydrase inhibitors.

Aim: A series of isocoumarin-chalcone hybrids were prepared and assays for the inhibition of four isoforms of human carbonic anhydrase (hCA; EC 4.2.1.1), hCA I, II, IX and XII. Materials & methods: Isocoumarin-chalcone hybrids were synthesized by condensing acetyl-isocoumarin with aromatic aldehydes. They did not significantly inhibit off-target cytosolic isoforms hCA I and II (KI >100 µM) but acted as low micromolar or submicromolar inhibitors for the tumor-associated isoforms hCA IX and XII. Results & conclusion: Our work provides insights into a new and scarcely investigated chemotype which provides interesting tumor-associated CA inhibitors, considering that some such derivatives like sulfonamide SLC-0111 are in advanced clinical trials for the management of metastatic advanced solid tumors.

A series of isocoumarin­chalcone hybrids was prepared and assays for the inhibition of four isoforms of the metalloenzyme carbonic anhydrase (CA; EC 4.2.1.1), i.e., human (h) isoforms hCA I, II, IX and XII. Isocoumarins were less investigated as inhibitors of this enzyme. Here we show that the isocoumarin­chalcone hybrids do not significantly inhibit the off-target cytosolic isoforms hCA I and II (K_Is >100 µM) but act as low micromolar inhibitors for the tumor-associated isoforms hCA IX and XII. Our work thus provides insights into a new and scarcely investigated chemotype which may provide interesting tumor-associated CA inhibitors, because some such compounds, e.g., the sulfonamide SLC-0111, are presently in advanced clinical trials for the management of metastatic advanced solid tumors.

Optimal cut-off value of procalcitonin and procalcitonin/albumin ratio for predicting bacteremia among patients living with cancer: a test-negative case-control study.

OBJECTIVE: The occurrence of bacteremia is critically important for the survival of cancer patients. Therefore, our study aims to evaluate the efficacy of procalcitonin (PCT) and the procalcitonin to albumin ratio (PAR) in predicting bacteremia among this population. METHODS: In this retrospective test-negative case-control study, we included 903 hospitalized cancer patients, divided into two groups: the bacteremia-positive group (BSI group, n = 384) and the bacteremia-negative group (non-BSI group, n = 519). We assessed the diagnostic significance of PCT and PAR through receiver operating characteristic (ROC) analysis and determined the optimal cut-off values using Youden's index. RESULTS: Both the duration of hospital stay and the 30-day mortality rate were significantly higher in the BSI group. The areas under the curve (AUC) for PAR and PCT were 0.749 (95% CI: 0.715-0.782) and 0.742 (95% CI: 0.708-0.776), respectively, indicating higher levels in the BSI group. The optimal cut-off values for predicting bacteremia were 0.72 for PAR and 1.32 for PCT. PAR showed the highest specificity (92.7%) and positive predictive value (PPV = 83.4%), while PCT demonstrated the highest sensitivity (51.3%) and negative predictive value (NPV = 71.6%). DISCUSSION: This study is the first in the literature to suggest that PAR and PCT are valuable biomarkers for diagnosing bacteremia in cancer patients. The identified cut-off values offer practical thresholds for bacteremia diagnosis.

The Clinical and Pathological Characteristics That Differentiate Cases With "Low Estrogen Receptor Expression" From Triple-Negative Breast Cancer.

Objective: Estrogen receptor (ER) expression is an immunohistochemical marker that is examined in all invasive breast cancers and has prognostic and predictive value. ER-positive breast cancers refer to those that show positivity for ER at 1% cellular expression or higher. The American Society of Clinical Oncology/College of American Pathologists guidelines suggest using the term "low ER-positive breast cancer" for tumors with ER expression between 1% and 10%. Low ER-positive breast cancers exhibit similarities, in terms of disease-free survival and overall survival rates, to triple-negative breast cancers (TNBCs) rather than ER-positive breast cancers. In this study, our aim was to compare the clinicopathological characteristics of low ER-positive breast cancer cases diagnosed and followed in our clinic with TNBCs. Materials and Methods: A total of 26 cases of low ER-positive breast cancer diagnosed at University of Health Sciences Turkey, Izmir Tepecik Training and Research Hospital between 2010 and 2016 were retrieved from hospital records. The relevant histopathology slides and blocks were retrieved and re-evaluated retrospectively through microscopic examination. Thirteen cases that met the criteria were included in the study. Additionally, a consecutive series of 13 TNBC cases that did not receive neoadjuvant treatment within the same time period were identified. Results: In the low ER-positive group, the presence of tumor necrosis, as well as histological grade, nuclear grade and Ki-67 proliferation index were significantly lower compared to the TNBC group. Ductal carcinoma in situ (DCIS) was significantly more common in the low ER-positive group compared to the TNBC group. There were no significant differences between the two groups in terms of tumor size, histological tumor type, axillary lymph node involvement, tumor margins, peritumoral and intratumoral inflammation, local recurrence, distant metastasis, survival, and other characteristics. Conclusion: Although our study consisted of a small number of cases, some features showed significant differences between low ER-positive breast cancers and TNBCs. Histological and nuclear grades, as well as the presence of a DCIS component, were associated with low ER-positive breast cancer. In contrast, the presence of tumor necrosis, as well as Grade 3 features and a high Ki-67 proliferation index indicated TNBC.

Isocoumarins: a new class of selective carbonic anhydrase IX and XII inhibitors.

Isocoumarins, isomeric to comarins which act as effective carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, were investigated for the first time as inhibitors of this enzyme. A series of 3-substituted and 3,4-disubstituted isocoumarins incorporating phenylhydrazone, 1-phenyl-pyrazole and pyrazolo-substituted pyrimidine trione/thioxo-pyrimidine dione moieties were investigated for their interaction with four human (h) CA isoforms, hCA I, II, IX and XII, known to be important drug targets. hCA I and II were not inhibited by these compounds, whereas hCA IX and XII were inhibited in the low micromolar range by the less bulky derivatives. The inhibition constants ranged between 2.7-78.9 µM against hCA IX and of 1.2-66.5 µM against hCA XII. As for the coumarins, we hypothesise that the isocoumarins are hydrolysed by the esterase activity of the enzyme with formation of 2-carboxy-phenylacetic aldehydes which act as CA inhibitors. Isocoumarins represent a new class of CA inhibitors.

Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study.

PURPOSE: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings. METHODS: Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. RESULTS: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). CONCLUSION: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

Efficacy and safety of bevacizumab in Turkish patients with metastatic and recurrent cervical cancer.

OBJECTIVE: To evaluate the efficacy of bevacizumab a monoclonal, antivascular endothelial growth factor antibody in combination with cytotoxic chemotherapy in Turkish patients with recurrent and metastatic cervical cancer. MATERIALS AND METHODS: Data of 64 patients with metastatic or recurrent cervical cancer, receiving bevacizumab with first-line cisplatin or carboplatin and paclitaxel chemotherapy between 2013 and 2017 were retrospectively evaluated. RESULTS: The mean age of the patients was 49 years (range, 28-68), the median follow-up time was 12 months (range, 2-53), the median progression-free survival (PFS) was eight months, and the median overall survival (OS) was 23 months. All 64 patients received a median of 6 (range, 1-12) bevacizumab and 6 (range, 2-12) chemotherapy cycles. The chemotherapy regimens used with bevacizumab were cisplatin and paclitaxel in 31 (48%) and carboplatin and paclitaxel in 33 (52%) patients. The survival in patients treated with bevacizumab and cisplatin plus paclitaxel was better-particularly in patients with no previous cisplatin-based radiosensitizer therapy-than those treated with carboplatin, paclitaxel, and bevacizumab (p=0.023). The bevacizumab dose was 7.5 mg/kg in 30 patients (47%) and 15 mg/kg in 34 patients (53%) every 21 days. No significant difference was reported in the OS and the PFS between the two groups. While the most common all-grades adverse events were nausea, neutropenia, anemia, and peripheral sensory neuropathy, the most common grade ≥3 adverse events were neutropenia, anemia, and peripheral sensory neuropathy. CONCLUSION: Adding bevacizumab to platinum and paclitaxel chemotherapy in a case of metastatic or recurrent cervical cancer is an effective and tolerable treatment for Turkish patients.

Programmed cell death ligand-1 expression in gastroenteropancreatic neuroendocrine tumors.

PURPOSE: Gastroenteropancreatic tumors (GEPNETs) is a heterogeneous disease with variable clinical course. While promising therapeutic options exist for other adult cancers, there are no new molecular-based treatments developed for GEPNETs. One of the main targets of cancer immunotherapy is the Programmed Cell Death Ligand-1 (PD-L1) pathway. Our purpose was to investigate the profile of PD-L1 expression in different organs of GEPNETs and compare the conventional immunohistochemistry (IHC) with the RNA expression analysis via real time polymerase chain reaction (RT-PCR) in order to determine which patients might be appropriate for immune check point-targeted therapy. METHODS: A total of 59 surgically or endoscopically resected GEPNET tissues were retrospectively collected. The expression of PD-L1 and mRNA was evaluated with IHC. RESULTS: The expression of PD-L1 was significantly associated with the high-grade classification (p=0.012). PD-L1 mRNA expression in tumor samples appeared to be higher compared to the corresponding normal tissues. In appendix, stomach and small intestine, the expression of PD-L1 mRNA was higher in the tumor tissues compared to the respective controls. In pancreas and colon, control tissues tend to have a higher PD-L1 mRNA expression compared to tumor tissues. PD-L1 mRNA expression was higher in GEP carcinomas (p=0.0031). CONCLUSION: RT-PCR was found to be more sensitive in detecting PD-L1 expression than conventional IHC. This study may provide an important starting point and useful background information for future research about immunotherapy for appendix, stomach and small intestine neuroendocrine carcinomas.

Biweekly cetuximab in combination with platinum and 5-fluorouracil in metastatic head and neck carcinoma.

BACKGROUND AND AIM: The combination of cetuximab with platinum and 5-fluorouracil (5-FU) chemotherapy prolongs survival in patients with metastatic or recurrent squamous-cell carcinoma of the head and neck (SCCHN). Biweekly (once in 2 weeks) administration of cetuximab requires fewer hospital visits and decreases treatment costs; therefore, it is more convenient both for the patients and for the healthcare providers. Here, we assessed the efficacy, safety, and tolerability of an alternative biweekly regimen of cetuximab in combination with platinum and 5-FU chemotherapy as a first-line treatment for these patients. METHODS AND MATERIALS: Medical records of patients with metastatic or recurrent non-nasopharyngeal SCCHN who were treated with a biweekly regimen of cetuximab (500 mg/m2 on day 1), cisplatin (40 mg/m2 on day 1) or carboplatin (target area under the curve 3.5 mg/ml × min on day 1), folinic acid (400 mg/m2 on day 1), and 5-FU (400 mg/m2 bolus on day 1 followed by continuous infusion of 2,400 mg/m2 5-FU over 46 h) were retrospectively reviewed. Survival estimates were calculated with the Kaplan-Meier method. RESULTS: In total, 60 patients were included. The median age of the patients was 60.5. The objective response rate was 53.3% (95% confidence interval [CI] = 40.7-65.9). The median progression-free survival duration was 6.8 months (95% CI = 5.5-8.1) and the median overall survival duration was 13.3 months (95% CI = 8.4-18.2). The most common grade 3 or 4 adverse events were neutropenia (28.3%) and leucopenia (13.3%). Grade 3 or 4 rash was observed in 3.3% of the patients. CONCLUSION: Biweekly administration of cetuximab, cisplatin, and 5-FU is an effective regimen with a favorable toxicity profile for the first-line treatment of metastatic or recurrent SCCHN. These results warrant further evaluation of this regimen in prospective trials.

Hormone receptor status and survival of medullary breast cancer patients. A Turkish cohort.

OBJECTIVES: To analyze the relationship between clinical features, hormonal receptor status, and survival in patients who were diagnosed with medullary breast cancer (MBC). Methods: Demographic characteristics, histopathological features, and survival statuses of 201 patients diagnosed with MBC between 1995 and 2015 were retrospectively recorded. Survival analyses were conducted with uni- and multivariate cox regression analysis. RESULTS: Median follow-up time was 54 (4-272) months. Median patient age at the time of diagnosis was 47 years old (26-90). Of the patients, 91.5% were triple negative. Five-year recurrence free survival time (RFS) rate was 87.4% and overalll survival (OS) rate 95.7%. For RFS, progesterone receptor (PR) negativity, atypical histopathological evaluation, absence of lymphovascular invasion, smaller tumor, lower nodal involvement were found to be favourable prognostic factors by univariate analysis (p less than 0.05). The PR negativity and smaller tumor were found to be favourable factors by univariate analysis (p less than 0.05). However, none of these factors were determined as significant independent prognostic factors for OS (p greater than 0.05).  Conclusion: Turkish MBC patients exhibited good prognosis, which was comparable with survival outcomes achieved in the literature. The PR negativity was related to a better RFS and OS rates.

Synthesis of well-defined bisbenzoin end-functionalized poly(ε-caprolactone) macrophotoinitiator by combination of ROP and click chemistry and its use in the synthesis of star copolymers by photoinduced free radical promoted cationic polymerization.

A new well-defined bisbenzoin group end-functionalized poly(ε-caprolactone) macrophotoinitiator (PCL-(PI)2) was synthesized by combination of ring opening polymerization (ROP) and click chemistry. The ROP of ε-CL monomer in bulk at 110 °C, by means of a hydroxyl functional initiator namely, 3-cyclohexene-1-methanol in conjunction with stannous-2-ethylhexanoate, (Sn(Oct)2), yielded a well-defined PCL with a cyclohexene end-chain group (PCL-CH). The bromination and subsequent azidation of the cyclohexene end-chain group gave bisazido functionalized poly(ε-caprolactone) (PCL-(N3)2). Separately, an acetylene functionalized benzoin photoinitiator (PI-alkyne) was synthesized by using benzoin and propargyl bromide. Then the click reaction between PCL-(N3)2 and PI-alkyne was performed by Cu(I) catalysis. The spectroscopic studies revealed that poly(ε-caprolactone) with bisbenzoin photoactive functional group at the chain end (PCL-(PI)2) with controlled chain length and low-polydispersity was obtained. This PCL-(PI)2 macrophotoinitiator was used as a precursor in photoinduced free radical promoted cationic polymerization to synthesize an AB2-type miktoarm star copolymer consisting of poly(ε-caprolactone) (PCL, as A block) and poly(cyclohexene oxide) (PCHO, as B block), namely PCL(PCHO)2.

Investigating KRAS/BRAF mutation in oropharyngeal squamous cell carcinomas: a preliminary study.

OBJECTIVES: This study aims to investigate the role of KRAS/BRAF gene mutation in the pathogenesis of oropharyngeal squamous cell carcinoma (OSCC). PATIENTS AND METHODS: A total of 26 OSCC patients (23 males, 3 females; mean age 60 years; range 41 to 77 years) diagnosed between January 2003 and November 2013 were included in the study. The methods used in our study were quantitative fluorescence polymerase chain reaction for KRAS/BRAF mutation analysis. RESULTS: Ten of the tumors were located at the tongue base, 12 in the tonsil and four at the floor of mouth. The mean tumor size was 3.8 cm. Six of the tumors were well differentiated, 18 were moderately differentiated and two were poorly differentiated. All cases were analyzed for KRAS and BRAF gene mutations and none of them showed gene mutations. CONCLUSION: We could not find any relation between OSCC and KRAS/BRAF gene mutations in our short case file. The role of mutations should be analyzed in larger series in OSCC to predict new targeted therapy modalities.

Does single receptor positive breast carcinoma differ with regard to age, tumor grade, and HER2 amplification status?

PURPOSE: To investigate whether there is a difference in patient and tumor characteristics in cases with single receptor positive (SRP) (ER-/PR+ and ER+/PR-) breast carcinoma in comparison with the double receptor positive (DRP) (ER+/PR+) and double receptor negative (DRN) (ER-/PR-) tumors. METHODS: A total of 255 breast cancer patients were categorized on the basis of their tumor hormonal receptor phenotype, age, grade, and HER2 amplification status. The study focused on the SRP phenotype (ER+/PR- and ER-/PR+) and compared it with the DRP (ER+/PR+rpar; and DRN (ER-/PR-) tumors. RESULTS: There were 103 (40.3%) DRP tumors, 98 (38.4%) DRN tumors and 54 (21%) SRP tumors, 41 (16.1%) of which were ER+/PR- and 13 (5.1%) were ER-/PR+. Compared to DRP tumors, the SRP group was more likely to be associated with grade 3 tumors and higher frequency of HER2 amplification status. ER-/PR+ tumors were more likely to be associated with younger age at diagnosis compared to ER+/PR- tumors. HER2 amplification, age, and grade were not significantly different between ER-/PR+ and DRN groups. Compared to the DRN group, the ER+/PR- group had lower grade. CONCLUSIONS: Our findings demonstrated that SRP phenotype including ER+/PR- and ER-/PR+ tumors is different from DRP group with regard to age, grade, and HER2 amplification status. Moreover, our data showed that ER-/PR+ tumors are associated with younger age.

Adjuvant chemotherapy may contribute to an increased risk for metabolic syndrome in patients with breast cancer.

PURPOSE: Cytotoxic treatment may cause weight gain and important alterations in the metabolic status of breast cancer (BC) patients. The aim of this study was to investigate the changes in metabolic and anthropometric parameters of patients with BC who received adjuvant chemotherapy. METHODS: All consecutive women treated with adjuvant TAC (docetaxel 75 mg/m(2), doxorubicine 50 mg/m(2), cyclophosphamide 500 mg/m(2)) chemotherapy for node-positive breast carcinoma at our Institution between 2008 and 2010 were included. RESULTS: Among 104 patients, 84 of them were stage II and 20 of them were stage III. When we compared the measurements between 1(st) and 6(th) adjuvant chemotherapy, we observed statistically significant increases in weight and serum triglyceride levels, and decreases in high density lipoprotein, apolipoprotein A-1, transferrin, albumin and prealbumin levels. An elevation of follicle stimulating hormone, luteinizing hormone together with the decrease of estradiol was detected. Waist-to-hip ratio has also increased significantly. In subgroup analyses, we observed dramatic changes in body mass index in pre-menopausal women whereas no significant change was seen in the post-menopausal group. CONCLUSIONS: Adjuvant chemotherapy may contribute to an increased risk for metabolic syndrome in patients with BC and these changes are more profound in pre-menopausal patients.

Octreotide in combination with AT-101 induces cytotoxicity and apoptosis through up-regulation of somatostatin receptors 2 and 5 in DU-145 prostate cancer cells.

Prostate cancer (PCa) is the most common type of cancer among males. Although survival rate of early-stage PCa is high, treatment options are very limited for recurrent disease. In this study, the possible synergistic cytotoxic and apoptotic effect of octreotide in combination with AT-101 was investigated in DU-145 hormone and drug refractory prostate cancer cell line. To enlighten the action mechanisms of the combination treatment, expression levels of somatostatin receptors 2 and 5 (SSTR2 and SSTR5) were also investigated. Cell viability was measured by XTT assay. Apoptosis was assessed through DNA fragmentation analysis and caspase 3/7 assay. mRNA and protein levels of SSTR2 and SSTR5 were evaluated by qRT-PCR and western blot analysis, respectively. Octreotide in combination with AT-101 inhibited cell viability and induced apoptosis synergistically in DU-145 cells as compared to any agent alone. Combination treatment increased both SSTR2 and SSTR5 mRNA and protein levels in DU-145 cells. The data suggest that this combination therapy may be a good candidate for patients with advanced metastatic PCa do not respond to androgen deprivation.

Capecitabine maintenance therapy following docetaxel/capecitabine combination treatment in patients with metastatic breast cancer.

The present study aimed to analyze the efficacy of maintenance therapy with single agent capecitabine for human epidermal growth factor receptor (HER2) negative metastatic breast cancer (MBC) patients following disease control with 6 cycles of docetaxel plus capecitabine chemotherapy as the first-line treatment. As an initial treatment, 6 cycles of docetaxel plus capecitabine followed by maintenance therapy with capecitabine were administered. A total of 55 patients received combination therapy and 48 patients proceeded to maintenance therapy: Of these, 32 patients (66.7%) were postmenopausal and 37 (77.1%) had estrogen and progesterone receptor positive disease. The median progression-free survival rate with maintenance therapy was 5.5 months (95% CI, 0-11.4 months) and the median overall survival (OS) was 26.6 months (95% CI, 21.8-30.1 months). The use of maintenance therapy improved previous responses in 4 patients (8.3%; 2 partial and 2 complete responses) and 32 patients (66.7%) had stable disease. The median number of maintenance therapy cycles applied was 6.5 (range 1-28, total 441). The observation of side effects, including grade 3/4 neutropenia, febrile neutropenia and fatigue was more common during combination therapy. The results of the present study indicate that maintenance with single agent capecitabine therapy is an effective and tolerable treatment option for HER2 negative MBC patients in which disease control with 6 cycles of docetaxel plus capecitabine chemotherapy is achieved in the first-line setting.

Are neutrophil/lymphocyte ratio and platelet/lymphocyte ratio associated with prognosis in patients with HER2-positive early breast cancer receiving adjuvant trastuzumab?

PURPOSE: To investigate whether the pretreatment neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) have any prognostic significance in patients with HER2-positive early breast cancer receiving adjuvant trastuzumab. METHODS: 187 patients were retrospectively analyzed. The patients were separated into two groups according to the mean value of NLR and PLR (low NLR≤2.38, high NLR>2.38; and low PLR≤161.28, high PLR>161.28, respectively). The relationship between pretreatment NLR, PLR and clinicopathological factors was investigated. Univariate and multivariate Cox regression analyses were performed. To evaluate survival rates, the Kaplan-Meier method with log rank test were used. RESULTS: The median duration of follow up was 26.0 months (range 6.0-84.0). In high NLR and PLR groups, the mean age was lower, tumor size was larger and the number of hormone receptor positive patients was higher. No statistically significant relationship was found between clinicopathological factors and both NLR and PLR groups. During follow up, the rate of relapse was 12.6% in the low NLR group, 16.2 % in the high NLR group, 12.6% in the low PLR group and 15.8% in the high PLR group (p=non significant). Although median disease free survival (DFS) was shorter in the high NLR than in the low NLR group, the difference was not statistically significant (p=0.45). No statistically significant difference was found between high and low PLR groups with regard to median DFS and overall survival (OS) (p=0.76, p=0.29, respectively). CONCLUSION: We conclude that in HER2-positive early breast cancer patients receiving adjuvant trastuzumab with high pretreatment NLR, DFS was shorter. As for PLR, no effect either on DFS or on OS was registered. Prospective studies with larger number of patients are required in order to evaluate the prognostic effect of NLR and PLR in HER2-positive breast cancer patients.

Allergic rhinitis and its relationship with autoimmune thyroid diseases.

BACKGROUND: Autoimmune thyroid diseases are the most common of all autoimmune diseases. In the literature, Hashimoto thyroiditis (HT) is considered to be a T-helper (Th) type 1 dominant condition, and Graves disease is considered a Th2-dominant condition. OBJECTIVE: The aim of this study was to highlight a new aspect of the relationships among Th cell subgroups by determining the incidence of autoimmune thyroid disease in patients with allergic rhinitis (AR). METHODS: Patients were diagnosed with AR based on their medical histories, physical examinations, and skin-prick test results in an outpatient clinic. The levels of free triiodothyronine, free thyroxine, thyroid-stimulating hormone, thyroid peroxidase antibodies, and thyroglobulin antibodies were measured in peripheral blood samples from all study subjects. RESULTS: A total of 1239 patients with AR and 700 consecutive, age- and sex-matched healthy subjects were included in the study. Thyroid function tests showed that 1037 patients with AR (83.7%) had normal thyroid function, 171 (13.8%) had euthyroid HT, and 31 (2.5%) had hypothyroid HT. Among the control subjects, thyroid function test results showed that 688 subjects (98.2%) had normal thyroid function, 10 subjects (1.4%) had euthyroid HT, and 2 subjects(0.4%) had hypothyroid HT. CONCLUSION: The incidence of HT in the general population is 1.5%; in contrast, it was observed in 16.3% of our patients with AR, which represented a much higher rate than that in the overall population. Graves disease was not detected in our study subjects. A high incidence of HT in patients with AR, in which Th2 responses are dominant, indicates that further studies of the relationships among atopy, autoimmune diseases, and Th cell subgroups are needed.

Docetaxel in combination with octreotide shows synergistic apoptotic effect by increasing SSTR2 and SSTR5 expression levels in prostate and breast cancer cell lines.

PURPOSE: Docetaxel (DTX) is widely used for the treatment of metastatic prostate and breast cancers. Despite the clinical success of DTX, drug-related cumulative toxicity restricts its clinical use in cancer therapy. Thus, there is an urgent need for new therapeutic options. Octreotide (OCT) is a synthetic somatostatin analog that induces apoptosis in different cancer cell lines in vitro. In this study, we investigated the possible synergistic apoptotic effects of DTX in combination with OCT in prostate and breast cancer cell lines. METHODS: The XTT cell viability assay was used to determine cytotoxicity. Apoptosis was evaluated by Cell Death Detection ELISA(Plus) Kit. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. Levels of SSTR2 and SSTR5 proteins were determined by western blot analysis. RESULTS: DTX and OCT combination induced apoptosis in both breast and prostate cancer cells in a concentration- and time-dependent manner. Moreover, combination treatment resulted in inhibition of anti-apoptotic proteins such as Bcl-2 and Bcl-xL and induction of pro-apoptotic proteins Bax, Cytochrome c and IAPs in all of the tested cancer cell lines. SSTR2 and SSTR5 protein levels were induced as compared to any agent alone. CONCLUSIONS: These results indicate that this combination treatment is a significant inducer of apoptosis in a synergistic manner in breast and prostate cancer cells. This strong synergism helps to lower the dose of DTX in both types of cancers, thus letting DTX to be used for longer periods by delaying resistance development and lesser side effects.

Patients with HER2-positive early breast cancer receiving adjuvant trastuzumab: clinicopathological features, efficacy, and factors affecting survival.

BACKGROUND: The aim of the present study was to evaluate clinicopathological characteristics of our early stage breast cancer patients who are epidermal growth factor receptor 2 (HER2) overexpressed/ amplified (HER2+), the efficacy of trastuzumab treatment and survival results. MATERIALS AND METHODS: Patients with HER2- positive early stage breast cancer receiving adjuvant trastuzumab were investigated retrospectively. Clinicopathological features of 210 patients and treatment outcome were analysed. To evaluate survival rates, the Kaplan-Meier method was used. Univariate and multivariate analyses were conducted with the Cox regression model. RESULTS: Mean age of the patients was 51.8, 71.9% being postmenopausal. Some 37.6% of patients were node negative, and 31% had T1 tumor size and 52.4% were positive for estrogen receptor. Of 210 patients, 89.5% completed planned 52 weeks adjuvant trastuzumab treatment. The median follow up was 27.5 months (6.0-86.0 ). Relapse free survival (RFS) was 68.0 months (95% CI: 62.1-74.0) and overall survival (OS) was 74.8 months (95% CI: 69.5-80.1). The 3 year OS for all patients was 92.0% and RFS was 79.6%. During follow up, relapse was detected at the rate of 14.3%. Trastuzumab associated cardiotoxicity was found at the rate of 3.3%. In univariate analyses, larger tumor size and grade III were significantly associated (p<0.05) with RFS. Multivariate analyses of covariates displaying p<0.05 identified grade III as an independent prognostic factor. CONCLUSIONS: In the present study, it was established that trastuzumab had a satisfactory safety profile and treatment efficacy as in other clinical studies and that among clinicopathological factors evaluated, only being grade 3 had a significant effect on RFS. The occurrence of relapse with adjuvant trastuzumab makes it necessary to identify molecular predictors, which will define this group better and help explain resistance to anti HER2 based therapies.