Piperlongumine increases the apoptotic effect of doxorubicin and paclitaxel in a cervical cancer cell line.

OBJECTIVE: Piperlongumine (PL) is an alkaloid derived from the edible pepper (Piper longum L) and it has been described to have various biologic activities including anticancer effects. Our aim in this study was to assess the cytotoxic role of PL on a cervical cancer cell line (HeLa) and to evaluate the effects of PL/doxorubicin and PL/paclitaxel combination therapies on apoptotic cancer cell death. MATERIAL AND METHODS: The cytotoxicity, IC50 doses by MTT assay confirmed by fluorescent imaging, and apoptotic cell rates by Annexin V staining using flow cytometry were determined for PL, doxorubicin, paclitaxel, and for their combinations. RESULTS: It was shown that the PL by itself induced the apoptosis in HeLa cells. PL in combination with doxorubicin and paclitaxel increased apoptotic cell death compared to either chemotherapeutic agent alone. CONCLUSION: We conclude that the PL inhibits cancer cell growth by inducing apoptosis and has a potential anticancer activity in cervical cancer, especially when combined with doxorubicin and paclitaxel.

Central nervous system metastatic epithelial ovarian cancer. Clinical parameters and prognostic factors: a multicenter study of Anatolian Society of Medical Oncology.

Central nervous system (CNS) metastasis is a rare event in the course of late stage epithelial ovarian cancer (EOC); however its incidence is increasing in parallel with prolonged survival of patients. OBJECTIVE: The authors assessed the clinical parameters and potential prognostic features in patients with CNS metastatic disease. MATERIALS AND METHODS: Clinical data of the 33 patients from the participating centers were retrospectively collected and analyzed. Median age at the time of CNS metastasis was 57 years. Median time from the diagnosis of primary EOC until CNS metastatic disease was 22 months. Nearly half (45.5%) of the patients had single CNS metastatic lesions and all patients in the study group except two received radiotherapy as palliative treatment. Median overall survival (OS) from the time of CNS metastasis was 15 months (0-66). At univariate analysis only number of brain metastatic lesions (p = 0.001) and presence of extracranial disease (p = 0.004) were strongly associated with OS whereas multimodal treatment, size of metastatic lesions, platinum sensitivity, age, grade, and disease stage at presentation were not. Development of CNS metastasis carries a poor prognosis, however patients with single metastatic lesions and only intracranial metastatic disease can have prolonged survival after appropriate palliative management of their disease.

Load transmission characteristics of limited carpal fusions: a two-dimensional finite element study.

Although limited carpal fusion is a choice of treatment in several wrist disorders, little is known about the biomechanics of these procedures, especially the loads carried by the ligaments. In a finite element study, four types of limited carpal fusions (scaphotrapeziotrapezoid, capitohamate, four corner fusion with and without scaphoid excision) were simulated and the loads carried by the ligaments were recorded. Measurements were repeated with and without implantation. The load transmission through the ligaments varied by the type of the fusion but, radioscaphoid and long radiolunate ligaments carried significantly more loads if not excised during the operation. Implantation did not affect the results in most cases. The model of the present study may be useful in preoperative planning.

Safety and tolerability of first-line bevacizumab in metastatic colorectal cancer.

PURPOSE: To determine the clinical features of bevacizumab-associated toxicities in metastatic colorectal cancer (MCRC) patients. METHODS: The medical records of 60 patients with MCRC who were treated with chemotherapy including bevacizumab in the first-line setting were retrospectively evaluated. RESULTS: Bevacizumab was administered along with irinotecan plus 5-fluorouracil7sol;leucovorin (5-FU/LV) to 44 patients, 57horbar;FU7sol;LV+oxaliplatin to 8 patients, capecitabine+oxaliplatin to 6 patients and 5-FU/LV to 2 patients. The total number of the cycles received was 381 (median 6, range 17horbar;13). The most common bevacizumab-related toxicity was grade 1-2 bleeding (28%) followed by hypertension (17%). Grade 1-2 proteinuria was seen in 8% of the patients (no grade 3-4 proteinuria). Arterial thromboembolic events (ATE) were not observed, however 3 patients (5%) had experienced grade 3-4 venous thromboembolic events. In 3 patients (5%) grade 1-2 wound complications were seen (delayed wound healing in the place of the venous access device in 2, and wound infection in 1). In addition, gastrointestinal perforation (GIP) was seen in 3 (5%) patients. Two of the patients were treated by surgical intervention and one patient died of sepsis. CONCLUSION: Bevacizumab is well tolerated when combined with various chemotherapy regimens. As bevacizumab is becoming widely used in the routine oncology practice, further studies which investigate the mechanism of bevacizumab-associated toxicities are warranted to develop effective management strategies for these adverse events.

ERCC1 is not expressed in hepatocellular cancer: A turkish oncology group, gastrointestinal oncology subgroup study.

PURPOSE: hepatocellular cancer (HCC) is a common malignancy with a high mortality rate. Existence of excisional repair cross complementation1 (ERCC1) is implicated in resistance to cisplatin treatment. Expression of ERCC1 in HCC is not known. In this study we aimed to find out whether a subset of HCC patients can be identified to benefit from cisplatin. METHODS: sixty-one patients with HCC who had enough tissue to do immunohistochemistry were identified in 3 institutions. Immunohistochemical staining was performed manually using the standard streptavidin-biotin-peroxidase method. Monoclonal anti-ERCC 1 (D-10) antibody from Santa Cruz Biotechnology (Santa Cruz, CA) was used. RESULTS: only one out of 61 patients (1.6%) had ERCC1 expression. CONCLUSION: although around 10% of HCC patients respond to cisplatin, this is unlikely to be due to ERCC1 negativity. Pathways other than ERCC1 should be searched to find ways to help these patients' treatment strategies.

Visceral adipose tissue as an indicator of insulin resistance in nonobese patients with new onset type 2 diabetes mellitus.

BACKGROUND: Obesity and type 2 diabetes mellitus are characterized by insulin resistance. We determined the relationship between insulin resistance and visceral adipose tissue (VAT) and their correlation with bioimpedance analysis in nonobese new onset type 2 diabetes patients. METHODS: A number of 30 new onset type 2 diabetes patients and 20 healthy control subjects with similar features, age between 45 - 72 years old, BMI < 27 kg/m (2), C-peptide > 0.6 nmol/L, were included in study. Fasting blood glucose, HbA1c, serum lipids, BMI, insulin, C-peptide, HOMA-IR, bioimpedance analysis and visceral and subcutaneous adipose tissue (by computed tomography) were measured. RESULTS: In the patient group, VAT was significantly higher compared to healthy control group (33.17 +/- 10.23 % vs. 16.53 +/- 7.85 %, p < 0.001). In the patient group VAT was correlated with HOMA-IR (r = 0.62, p = 0.003), but no significant correlation was observed between VAT and bioimpedance analysis. CONCLUSIONS: The amount of VAT is significantly higher in nonobese new onset patients with type 2 diabetes than the healthy control group. In these patients, VAT measured by CT is an important indicator of insulin resistance. Although bioimpedance analysis can give an idea about total body fat and obesity, it is not sufficient in evaluating fat distribution and therefore is not effective in predicting insulin resistance.

Normal range of motion of the joints of the upper extremity in male subjects, with special reference to side.

We measured, with a universal full-circle manual goniometer, the active and passive arcs of motion of the shoulder, elbow, forearm, and wrist in 1000 healthy male subjects who were right-hand dominant and who ranged in age from eighteen to twenty-two years. The ranges of motion on the right side were significantly smaller than those on the left. We concluded that the contralateral, normal side may not always be a reliable control in the evaluation of restriction of motion of a joint.

Patellectomy with vastus medialis obliquus advancement for comminuted patellar fractures: a prospective randomised trial.

We have compared the results of simple patellectomy (group A, n = 16) and patellectomy with advancement of the vastus medialis obliquus (group B, n = 12) in a prospective, randomised trial, with a minimum follow-up of three years. The results in group B were significantly better (p < 0.001) than those in group A. Although the patella should be preserved if possible, we advocate advancement of the vastus medialis obliquus when patellectomy is necessary.

Trapezio-lunate external fixation for scaphoid fractures. An experimental and clinical study.

Trapezio-lunate external fixation for scaphoid fractures has been investigated experimentally and clinically. Six below-elbow fresh amputation specimens in which proximal, waist and distal scaphoid fractures were created, displaced, reduced and externally fixed were used for an experimental study and after 10,000 extension-flexion movements of the wrist, no displacement was observed. A strain-gauge study confirmed the strains at the fracture site. Seven patients were treated in this way. No immobilization was necessary and all patients returned to their regular employment within 3 days and all fractures were united without displacement. The technique overcomes certain disadvantages of plaster fixation and internal fixation of scaphoid fractures.

Avascular necrosis of the scaphoid treated by total excision and radial advancement osteotomy.

Total scaphoid excision and radial advancement osteotomy has been investigated in a cadaveric and clinical study. In three below-elbow fresh amputation specimens, the technique was utilized and stability was checked by radiographs. Instability on ulnar deviation was prevented by extensor carpi radialis longus tenodesis. Four patients were treated in this way. The wrist was immobilized in a below-elbow splint for 45 days, then active motion was encouraged. After 10 months, three patients had excellent results and one patient had good result using the criteria of Cooney et al (1987).

Various manifestations of hyperphalangism.

Hyperphalangism is a rare congenital anomaly, with an extra phalanx between the phalanges in a finger. About 100 cases have been recorded in the literature. We report 42 cases in six generations of a family with various manifestations.

Medium-term results of trapezio-lunate external fixation for scaphoid fractures.

We treated 36 scaphoid fractures in 34 patients with trapezio-lunate external fixation. According to the Herbert and Fisher classification, there were 16 type B1, 14 type B2, four type B3 and two type B4 fractures. Trapezial and lunate pins broke in three patients and these were rated as failures. The remaining 33 fractures were followed-up for 3 years and all had excellent outcomes, without signs of arthritis, avascularity or instability.

Calcitonin inhibits heterotopic bone formation in rats.

The effect of salmon calcitonin on heterotopic bone formation in rats was analysed. Thirty days after implantation of demineralized bone matrix, the weights of implants from animals receiving calcitonin were reduced, in contrast to the increase shown in the untreated control group. In the control group, the implants were visible on roentgenograms at the 20th day and histologic examination revealed new bone formation, whereas in the calcitonin-treated group the implants were never visible on roentgenograms throughout the study and only remnants of implants could be detected histologically. This study suggests that calcitonin inhibits heterotopic bone formation in rats.

Treatment of severe residual clubfoot deformity by trans-midtarsal osteotomy.

This study reviews the preliminary results of transmidtarsal osteotomy performed on 11 patients (12 feet) who previously underwent surgery for resistant clubfoot and needed further surgery for severe residual deformities. Opening wedge medial cuneiform osteotomy, closing wedge cuboid osteotomy, and truncated wedge middle and lateral cuneiform osteotomy were performed. The procedure was performed initially on normal cadaver feet. The average improvement of anteroposterior talo-first metatarsal angle was 20 degrees and lateral calcaneo-first metatarsal angle was 16 degrees. The authors conclude that with this simple procedure, angular and rotational correction in three planes can be obtained simultaneously in severe residual clubfoot deformity without the need for extensive soft tissue release.

Assessment of variations in the measurement of hip ultrasonography by the Graf method in developmental dysplasia of the hip.

The purpose of this study was to assess the variations in the measurement of hip ultrasonography using the Graf method in developmental hip dysplasia. Twenty-two observers independently analyzed 20 hip ultrasonograms on two occasions. Intraobserver and interobserver agreement ratios on the exact Graf classification were 65% and 51%, respectively. Intraobserver and interobserver agreement ratios on the treatment method according to the hip type were 76% and 64%, respectively. Average intraobserver and interobserver differences were 4.0 degrees and 5.1 degrees for the alpha angle, and 5.9 degrees and 10.1 degrees for the beta angle, respectively. It was concluded that having a basic knowledge of the Graf method was the key point, and the observer's previous number of examinations had no effect on the results.

[In vitro evaluation of antibiotic diffusion from antibiotic impregnated xenografts]. / Evaluation in vitro de la diffusion des antibiotiques à partir d'une xénogreffe imprégnée d'antibiotiques.

PURPOSE OF THE STUDY: The purpose of the study was to evaluate xenografts as a slow release antibiotic delivery system, as xenografts also have excellent biocompatibility and osteogenesis-stimulating effect. MATERIAL: Xenograft (Unilab Surgibone) blocks of 5 x 5 x 5 mm were used in the study. Antibiotics used for impregnation were gentamicin sulphate, ciprofloxacin and penicillin G. METHODS: In the pilot study, xenograft blocks impregnated with gentamicin sulphate solution and the contact time was between 1/2 to 10 hours. Then the grafts were incubated and the antibiotic concentration was measured in the elution fluid changed every day. The minimum contact time to release the antibiotic 10 days over 0.5 microgram/ml was 8 hours. The 8 hours contact time was used in the main study to evaluate gentamicin sulphate, ciprofloxacin and penicillin G. The method was the same as in the pilot study. RESULTS: All antibiotics showed similar release patterns reaching their peaks on the 5th day and then gradually decreasing below the effective level (0.5 microgram/ml) approximately on day 10. DISCUSSION: Although various materials have been used to deliver antibiotics, they have some certain disadvantages especially reduced biocompatibility. The superiority of xenografts over other materials, is not only biocompatibility but also to facilitate osteogenesis. The only objection may be the relatively short duration of release (10 days) but the length of antibiotherapy is controversial and standard 6 weeks of administration has no documented superiority over other time intervals. CONCLUSION: Our delivery system is superior to others as its function is not only to deliver antibiotics but has its place in orthopedic practice to fill defects and stimulate osteogenesis. Also the preparation of this system is not time and skill consuming.

Percutaneous autologous bone marrow grafting for simple bone cysts.

Twelve patients with simple bone cysts treated by percutaneous autologous bone marrow grafting were studied prospectively to evaluate the radiographic healing of the cysts, complications, and clinical outcome. The procedure included percutaneous aspiration of the cyst's fluid and the injection of the autologous bone marrow into the cyst cavity, which was aspirated from the posterior iliac crest. The mean volume of the lesions was 51.2 cubic centimeters (27 to 74 cc). The mean follow-up time was 23 months (range: 18 to 38 months). Complete healing occurred in two of the patients. Three cysts had residual cystic defect in which two required curettage and bone chip grafts. Six cases recurred. One patient failed to show any signs healing. We concluded that factors such as the size, multi-loculation, and completeness of the filling of the cyst with bone marrow grafting might influence the postoperative results of the treatment of simple bone cysts with bone marrow injection. We found more favorable result with unilobular, small cysts. Therefore, we believe that this method of treatment should be applied to carefully selected patients.

Comparison of second-line treatment outcomes between sensitive and refractory small cell lung cancer patients: a retrospective analysis.

PURPOSE: Small cell lung cancer (SCLC) has a high relapse rate despite being very chemosensitive. The efficacy of second-line treatment is dismal. Our aim was to evaluate the outcome of second-line treatment. METHODS: We retrospectively assessed data of 120 SCLC patients who failed first-line treatment and received second-line treatment at three medical oncology centers. RESULTS: Median age of group was 58. 82 % had an ECOG PS of 0-1 at the time of relapse. 39 % were at limited stage (LS) at the time of diagnosis. Patients who progressed more than 3 months after first-line therapy were categorized as having platinum-sensitive disease (PSD) (64 %). The number of patients who received platin-based combination treatment was 33 (27 %). The median OS time starting from the initiation of second-line treatment was 7 months. Multivariate analysis identified PS (p = 0.006), extent of disease at diagnosis (0.014) and PSD (0.001) as the independent prognostic factors for survival. Subgroup analyses of the patients with PSD indicated platin rechallenge yields higher progression-free survival, overall survival and overall response rate. CONCLUSION: Patients with good ECOG PS,who have PSD or initially presenting with LS, have a good prognosis and in patients with PSD, platinum-based therapy would be more appropriate.