Does Rotation and Anterior Translation Persist as Residual Instability in the Knee after Anterior Cruciate Ligament Reconstruction? (Evaluation of Coronal Lateral Collateral Ligament Sign, Tibial Rotation, and Translation Measurements in Postoperative MRI).

Purpose: The aim of this study was to evaluate the presence of residual instability in the knee after ACL reconstruction through the analysis of MRI findings. Methods: This study included patients who underwent isolated ACL reconstruction between December 2019 and December 2021, and had preoperative and postoperative MRI, clinical scores, and postoperative isokinetic measurements. The anterior tibial translation (ATT) distance, coronal lateral collateral ligament (LCL) sign, and femorotibial rotation (FTR) angle were compared preoperatively and postoperatively. The correlation between the changes in preoperative-postoperative measurements and postoperative measurements with clinical scores and isokinetic measurements was examined. The clinical outcomes were compared based on the presence of a postoperative coronal LCL sign. Inclusion criteria were set as follows: the time between the ACL rupture and surgery being 6 months, availability of preoperative and postoperative clinical scores, and objective determination of muscle strength using isokinetic dynamometer device measurements. Patients with a history of previous knee surgery, additional ligament injuries other than the ACL, evidence of osteoarthritis on direct radiographs, cartilage injuries lower limb deformities, and contralateral knee injuries were excluded from this study. Results: This study included 32 patients. After ACL reconstruction, there were no significant changes in the ATT distance (preoperatively: 6.5 ± 3.9 mm, postoperatively: 5.7 ± 3.2 mm) and FTR angle (preoperatively: 5.4° ± 2.9, postoperatively: 5.2° ± 3.5) compared to the preoperative measurements (p > 0.05). The clinical measurements were compared based on the presence of a postoperative coronal LCL sign (observed in 17 patients, not observed in 15 patients), and no significant differences were found for all parameters (p > 0.05). There were no observed correlations between postoperative FTR angle, postoperative ATT distance, FTR angle change, and ATT distance change values with postoperative clinical scores (p > 0.05). Significant correlations were observed between the high strength ratios generated at an angular velocity of 60° and a parameters FTR angle and ATT distance (p-values: 0.028, 0.019, and r-values: -0.389, -0.413, respectively). Conclusions: Despite undergoing ACL reconstruction, no significant changes were observed in the indirect MRI findings (ATT distance, coronal LCL sign, and FTR angle). These results suggest that postoperative residual tibiofemoral rotation and tibial anterior translation may persist; however, they do not seem to have a direct impact on clinical scores. Furthermore, the increase in tibial translation and rotation could potentially negatively affect the flexion torque compared to the extension torque in movements requiring high torque at low angular velocities.

N-Propargylic ß-enaminones in breast cancer cells: Cytotoxicity, apoptosis, and cell cycle analyses.

Breast cancer is one of the most common cancers worldwide and the discovery of new cytotoxic agents is needed. Enaminones are regarded to be a significant structural motif that is found in a variety of pharmacologically active compounds however the number of studies investigating the anticancer activities of N-propargylic ß-enaminones (NPEs) is limited. Herein we investigated the potential cytotoxic and apoptotic effects of 23 different NPEs (1-23) on human breast cancer cells. Cytotoxicity was evaluated via MTT assay. Apoptotic cell death and cell cycle distributions were investigated by flow cytometry. CM-H2DCFDA dye was used to evaluate cellular ROS levels. Expression levels of Bcl-2, Bax, p21, and Cyclin D1 were measured by quantitative real-time PCR. ADME properties were calculated using the ADMET 2.0 tool. NPEs 4, 9, 16, and 21 showed selective cytotoxic activity against breast cancer cells with SI values >2. NPEs induced apoptosis and caused significant changes in Bcl-2 and Bax mRNA levels. The cell cycle was arrested at the G0/G1 phase and levels of p21 and Cyclin D1 were upregulated in both breast cancer cells. ROS levels were significantly increased by NPEs, suggesting that the cytotoxic and apoptotic effects of NPEs were mediated by ROS. ADME analysis revealed that NPEs showed favorable distributions in both breast cancer cell lines, meaning good lipophilicity values, low unfractionated values, and high bioavailability. Therefore, these potential anticancer compounds should be further validated by in vivo studies for their appropriate function in human health with a safety profile, and a comprehensive drug interaction study should be performed.

Endoplasmic Reticulum Stress-Induced Apoptotic Effects of Novel 1-Pyrroline (3,4-Dihydro-2H-pyrrole) Derivatives on Breast Cancer Cells.

Heterocyclic compounds have emerged as promising and appealing scaffolds for developing effective antitumor agents. Here, the effects of synthesized 24 different 1-pyrroline derivatives (PDs) containing substituted aryl sulfide moiety were investigated on human breast cancer cell lines. The viability of cells was assessed via MTT assay. Reactive oxygen species (ROS) generation was analyzed via fluorescent dye CM-H2DCFDA. Apoptotic cells were determined via flow cytometry. Endoplasmic reticulum (ER) stress-associated protein levels were analyzed via western blot analysis. Four of the PDs (PD-12, -14, -16 and -17) had great cytotoxic selectivity against breast cancer cells. Apoptotic cell death was induced by PDs via the generation of ROS. PDs significantly increased the GRP78, p-PEAK, p-eIF2α, and CHOP protein levels indicating ER stress in breast cancer cells. These results imply that newly synthesized PDs may be potential anticancer agents as they selectively inhibit breast cancer cells.

Synthesis of 3-[(4-Nitrophenyl)thio]-Substituted 4-Methylene-1-pyrrolines from N-Propargylic ß-Enaminones.

A facile and efficient method for the synthesis of 3-[(4-nitrophenyl)thio]-substituted 4-methylene-1-pyrrolines is described. When treated with 4-nitrobenzenesulfenyl chloride in refluxing acetonitrile, N-propargylic ß-enaminones produced α-sulfenylated N-propargylic ß-enaminones, which, in the presence of sodium hydride or cesium carbonate, underwent nucleophilic cyclization to afford 4-methylene-3-[(4-nitrophenyl)thio]-1-pyrrolines in good to high yields. It was shown for the first time that on N-propargylic ß-enaminone systems, α-sulfenylation dominates over the formation of thiirenium ion. This one-pot two-step process was found to be general for a variety of N-propargylic ß-enaminones and demonstrated good tolerance to a diversity of aromatic and heteroaromatic groups with electron-withdrawing and electron-donating substituents. This process is also applicable to the cyclization of internal alkyne-tethered N-propargylic ß-enaminones. The enrichment of 1-pyrroline core with an aryl sulfide moiety might exhibit potential for the synthesis of molecules of pharmacological interest.

Is post-treatment standardized uptake value a prognostic factor in unresectable non-small cell lung carcinoma?

Aim Concurrent chemoradiotherapy (CRT) is the standard of care for locally advanced, unresectable non-small cell lung carcinoma (NSCLC). The aim of this study was to assess the prognostic value of maximum standardized uptake values (SUVmax) in patients with unresectable stage III NSCLC treated with concurrent CRT. Method 18F-FDG PET-CT scans were obtained before and after treatment in patients with unresectable stage III NSCLC treated with concurrent CRT. To determine the prognostic value of SUVmax of the primary tumor (PT), univariate and multivariate Cox regression model were carried out. Results Between January 2008 and December 2013, this study included 43 patients (median age 56 years, 95% male). Univariate analysis showed that having a high post-treatment PT-SUVmax was associated with a higher risk of death and having a high post-treatment PT-SUVmax with a higher risk of disease recurrence. Multivariate analysis showed that having a low post-treatment PTSUVmax (cut off 3.9) was associated with longer overall and progression free survival (HR 8.55, 95% CI; 2.56-28.55, p=0.000 and HR 2.854, 95% CI; 1.43-5.67, p=0.003, respectively). Conclusion Post-treatment PT-SUVmax may be an independent prognostic factor in patients with unresectable stage III NSCLC treated with concurrent chemoradiotherapy.

Carboplatin and etoposide followed by once-daily thoracic radiotherapy in limited disease small-cell lung cancer: unsatisfactory results.

AIMS AND BACKGROUND: There has been a trend to replace cisplatin with carboplatin in the treatment of small-cell lung carcinoma. The goal of the present study was to determine the efficacy of carboplatin and etoposide followed by thoracic radiotherapy in patients with previously untreated limited disease small-cell lung carcinoma. METHODS: From February 2001 to March 2007, 47 patients with limited disease small-cell lung cancer were enrolled in the study. Etoposide, 100 mg/m2, was administrated intravenously on days 1-3 in combination with carboplatin, AUC 6, on day 1 every 21 days for 6 cycles. In cases considered to have non-progressive disease following induction chemotherapy, thoracic radiotherapy was given with in a once daily fraction of 2.0 Gy, 5/wk, up to 50-60 Gy. RESULTS: Forty-one patients were evaluated. Median age was 62 (range, 40-78), 88% of patients were male. ECOG PS was 0-1 in 38 patients. Seven of the 41 patients (17.5%) had pleural effusion (one malignant) and 7 patients (17.5%) had involved supraclavicular lymph nodes. Ninety percent of patients had elevated serum lactate dehydrogenase levels. Median follow-up was 13.5 mo. A total of 209 cycles of chemotherapy was administered (median, 6; range, 1-6). Thoracic irradiation was given to 33 patients. The overall response rate to combined modality on an intention-to-treat basis was 73%. Median survival time was 13.7 months (95% CI, 10.3-17.1), and median progression-free survival was 9.5 months (95% CI, 8.6-10.4). Two- and four-year overall survival was 23% and 7%, respectively. Grade 3-4 neutropenia and leukopenia were the most common adverse events and occurred in 46.0% and 24.0% of the patients, respectively. Six (14%) patients experienced febrile neutropenia. Three patients (7%) died of sepsis and neutropenic fever. Non-hematological toxicities were mild. CONCLUSIONS: Carboplatin and etoposide chemotherapy followed by thoracic radiotherapy in LD-SCLC appears to be unsatisfactory.

Development of a coprecipitation system for the speciation/preconcentration of chromium in tap waters.

A method for the speciation of chromium(III), chromium(VI) and determination of total chromium based on coprecipitation of chromium(III) with dysprosium hydroxide has been investigated and applied to tap water samples. Chromium(III) was quantitatively recovered by the presented method, while the recovery values for chromium(VI) was below 10%. The influences of analytical parameters including amount of dysprosium(III), pH, centrifugation speed and sample volume for the quantitative precipitation were examined. No interferic effects were observed from alkali, earth alkali and some transition metals for the analyte ions. The detection limits (k=3, N=15) were 0.65 microg/L for chromium(III) and 0.78 microg/L for chromium(VI). The validation of the presented method was checked by the analysis of certified reference materials.

Comparison of inflammatory breast cancer and noninflammatory breast cancer in Western Turkey.

OBJECTIVE: The study was aimed at investigating the clinical and biological features and survival outcomes of patients who were treated for metastatic inflammatory and noninflammatory breast carcinoma. SUBJECTS AND METHODS: One hundred and sixty-seven metastatic breast cancer patients were enrolled into this study and divided into two groups: inflammatory (n = 46) and noninflammatory (n = 121). The clinical and hormone receptor status, c-erbB-2, Ki-67, and p53 expression, based on the immunohistochemical staining patterns, were compared between the two groups. RESULTS: The inflammatory breast carcinoma group had a younger patient population, higher rate of adjuvant anthracycline therapy, number of lymph node metastases, rates of extranodal extension and c-erbB-2 overexpression than noninflammatory breast cancer patients (p < 0.05). With regard to survival, there were slightly better outcomes in the noninflammatory breast carcinoma group (30 months) compared to the inflammatory breast carcinoma group (23 months), but the difference was not statistically significant (p = 0.08). While survival results of p53-negative inflammatory and noninflammatory breast carcinoma patients were similar, p53-positive survival was significantly worse (p < 0.05) in inflammatory breast cancer carcinoma patients. CONCLUSION: Because of c-erbB-2 overexpression in inflammatory breast carcinoma patients, treatment options including trastuzumab could have given better survival outcomes. Survival of inflammatory breast carcinoma patients with a low p53 immunohistochemistry staining appeared similar to that for noninflammatory breast carcinoma. For this reason, new treatment options are needed especially in inflammatory breast carcinoma patients with high p53 positivity.

Patterns of care for lung cancer in radiation oncology departments of Turkey.

PURPOSE: To determine the patterns of care for lung cancer in Turkish radiation oncology centers. METHODS AND MATERIALS: Questionnaire forms from 21 of 24 (87.5%) centers that responded were evaluated. RESULTS: The most frequent histology was non-small cell lung cancer (NSCLC) (81%). The most common postoperative radiotherapy (RT) indications were close/(+) surgical margins (95%) and presence of pN2 disease (91%). The most common indications for postoperative chemotherapy (CHT) were ">/= IB" disease (19%) and the presence of pN2 disease (19%). In Stage IIIA potentially resectable NSCLC, the most frequent treatment approach was neoadjuvant concomitant chemoradiotherapy (CHRT) (57%). In Stage IIIA unresectable and Stage IIIB disease, the most frequent approach was definitive concomitant CHRT (91%). In limited SCLC, the most common treatment approach was concomitant CHRT with cisplatin+etoposide for cycles 1-3, completion of CHT to cycles 4-6, and finally prophylactic cranial irradiation in patients with complete response (71%). Six cycles of cisplatin + etoposide CHT and palliative thoracic RT, when required, was the most commonly used treatment (81%) in extensive SCLC. Sixty-two percent of centers did not have endobronchial brachytherapy (EBB) facilities. CONCLUSION: There is great variation in diagnostic testing, treatment strategies, indications for postoperative RT and CHT, RT features, and EBB availability for LC cases. To establish standards, national guidelines should be prepared using a multidisciplinary approach.

Comparison of the clinical and pathological features between patients with recurrent metastatic breast carcinoma and patients with initially metastatic breast carcinoma.

OBJECTIVE: To compare initial metastatic breast carcinoma (MBC) with recurrent MBC and assess their biologic phenotypes and clinical behaviors. METHODS: A comparison of clinical and biological characteristics and median overall survival times were assessed in the 251 patients with MBC at the Division of Medical Oncology, Ege University School of Medicine, and the Division of Radiation Oncology, Tepecik Government Hospital, Izmir, Turkey between 1995 and 2004. Hormone receptors, c-erbB-2, Ki-67, and p53 expressions were performed by immunohistochemistry. RESULTS: Out of 251 MBC patients, 206 patients had recurrent MBC, and 45 had initial MBC. Regarding survival, there was no difference between the recurrent MBC group and the initial MBC group. The initial MBC group had a higher proportion of T4 tumors (46% versus 27%), a lower proportion of T1-2 tumors (31% versus 55%; p=0.01), and a higher percentage of patients with high Ki-67 expression (64% versus 49%; p=0.05). Multivariate analysis showed that T stage was an independent prognostic factor (p=0.02). CONCLUSION: Patients with initial MBC tended to present with larger tumors. This relationship can be explained by delayed diagnosis. The potential for reducing death rates from breast cancer is contingent on educational improvement and increased screening rates.