Effect of hypericin on the ADAMTS-9 and ADAMTS-8 gene expression in MCF7 breast cancer cells.

AIM: To investigate the effects of hypericin which is obtained from the plant Hypericum perforatum on the expression and the regulation of ADAMTS8 and ADAMTS9 genes in MCF7 breast cancer cells and on the viability of these cells. MATERIALS AND METHODS: MCF7 cells were cultured and were separately exposed to 2, 10 and 50 µl/mL of hypericin. After 24 hours, RNA was isolated from these cells and converted to cDNA. The expression levels of ADAMTS8 and ADAMTS9 genes were evaluated using the Reverse Transcription Polymerase Chain Reaction. XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide, disodium salt) cell viability assay was used to determine cytotoxicity. RESULTS: ADAMTS9 expression in MCF7 cells were increased 1.8 and 3.6 fold with the use of 2 and 10 µl/mL of hypericin, respectively; and decreased 0.7 fold with the use of 50 µl/mL of hypericin. There was no significant change in the ADAMTS8 expression. Rapid cell death was observed in the cancer cells when hypericin was used at a dose of ≥ 50 µl/mL. CONCLUSIONS: The increase in ADAMTS9 expression can be a useful factor in the prevention of possible metastasis in breast cancer and for the occurrence of a tumor suppressive effect. Hypericin increases the expression of ADAMTS9, therefore, it may show its antitumoral and antiapoptotic effects by means of ADAMTS9.

Duration of anti-HER2 blockage therapy may improve survival in HER2 positive metastatic breast carcinoma patients.

PURPOSE: The duration of anti-HER2 blockage therapy in metastatic breast cancer patients is still unclear. We aimed to evaluate the effect of the anti-HER2 blockage therapy duration and other factors on survival in HER2 positive metastatic breast carcinoma (MBC) patients. METHODS: The medical records of 193 HER2 positive MBC patients, who did not have the opportunity to receive adjuvant trastuzumab therapy but had received trastuzumab in the metastatic setting were retrospectively evaluated. RESULTS: The median age at diagnosis was 45.0 years (range 21-83). Ninety-two (47.7%) patients received palliative trastuzumab < 6 months median, whereas 101 patients received trastuzumab ≥ 6 months median. The median number of trastuzumab cycles was 8 (range 1-51). Median survival after breast cancer recurrence was 31.0 months (range 24.3-37.7). The duration of trastuzumab therapy had a significant impact on the prognosis of recurrent breast cancer (22.0 vs 49.0 months, for ≤ 6 months of treatment duration, respectively; p<0.0001). Survival after breast cancer recurrence for the patients who received lapatinib plus capecitabine vs those who did not was significantly different (59 patients, p=0.005). Moreover, there was a statistically significant relationship between prolonged lapatinib plus capecitabine combination therapy and improved survival after disease recurrence (p=0.022). In the multivariate Cox regression analysis, treatment with trastuzumab > 6 months (p=0.003) was the only independent prognostic factor for survival after breast cancer recurrence. CONCLUSION: The duration of anti-HER2 blockage therapies, especially with trastuzumab, seems to improve survival of HER2-positive metastatic breast cancer patients who were not previously treated with adjuvant trastuzumab, regardless of other therapies.

Sequential adjuvant docetaxel and anthracycline chemotherapy for node positive breast cancers: a retrospective study.

PURPOSE: Anthracyclines and taxanes are the most active agents in the adjuvant treatment of breast cancer (BC). They can be used simultaneously or sequentially. The optimal schedule and duration for their administration is unknown. We analyzed the efficacy of sequential adjuvant anthracycline and docetaxel administration in node positive BC patients. METHODS: Node positive BC patients (N=539) from 6 medical oncology centers in Turkey who received sequential adjuvant anthracycline-based regimens and taxane chemotherapy were included in this study between 2006 - 2010. One-hundred and thirty-eight (25%) patients received 3 cycles of anthracycline-based chemotherapy followed by 3 cycles of docetaxel (3+3) and 401 (75%) patients received 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel (4+4). Prognostic factors analyzed were estrogen receptor (ER), progesterone receptor (PR), HER2, tumor grade, and nodal status in relation to disease free survival (DFS) and HER2 status in relation to overall survival (OS). RESULTS: The patient median age was 48 years (range 18-79). Most common grade 3-4 toxicities were neutropenia, mucositis and arthralgia. No treatment-related toxic deaths were seen. With a median follow up of 26 months (range 1-115) 61 (11.3%) recurrences and 11 (2%) deaths were registered. Three-year DFS was 81% and OS 96% for all patients. There was no statistically significant difference between 3+3 and 4+4 groups in terms of survival (3-year DFS 88% and 79% [p=0.28] and OS 97% and 95% [p=0.60), respectively). CONCLUSION: Sequential chemotherapy with 4+4 cycles of anthracycline and docetaxel every 3 weeks is an acceptable regimen for adjuvant treatment of node positive BC patients. Duration of chemotherapy should be planned depending on prognostic factors. In this study there was no difference between 3+3 and 4+4 groups in DFS and OS despite the presence of good prognostic factors in the 3+3 group.

Multiple primary malignant neoplasms: multi-center results from Turkey.

PURPOSE: Multiple primary malignant neoplasms (MPMNs) are defined as a diagnosis of two or more indepen-dent primary malignancies of different histologies/origins in an individual. The frequency of MPMN is being increasing. In this study we aimed to determine the frequency and clinical features of second primary cancers (SPCs). METHODS: From January 1990 to December 2010, patients with MPMNs were screened in 5 centers. Data were obtained retrospectively from hospital charts. RESULTS: Three hundred seventy-seven patients with MPMNs were evaluated. The median age at initial cancer diagnosis was 61 years (range 18-88). The median age at second cancer was 64 years (range 20-89). The median time between two cancer diagnoses was 15 months (range 0-504). Male to female ratio was 1.44 (M/F 223/154). The most frequent initial cancer types were head and neck (54 patients, 14.3%), breast (54 patients, 14.3%), and colorectal (43 patients, 11.4%). The most frequent second cancer types were lung (76 patients, 20.2%), colorectal (39 patients, 10.3%) and breast (33 patients, 8.8%). The most common cancer pairs in females were breast-gynecologic cancers (15 patients, 9.7%), colorectal-breast cancers (9 patients, 5.8%) and breast-colorectal cancers (7 patients, 4.5%). The most common cancer pairs in males were head and neck-lung cancers (29 patients, 13%), bladder-lung cancers (9 patients, 4%), and bladder-prostate cancers (7 patients, 3%). The median follow up was 36 months (range 17horbar;595). CONCLUSION: Physicians should be aware of SPCs probabilities. Newly developed suspicious lesions should be evaluated rigorously. Histopathologic evaluations of suspicious lesions for second tumors should be used extensively if needed. In our series, the most common pairs were breast-gynecologic cancers in females and head and neck-lung cancers in males.

Does ureteral access sheat usage lead to permanent damage in the ureter? A placebo controlled trial in a rabbit model

Abstract Purpose: To evaluate the clinical stenosis or precursor histological changes that ureteral access sheaths commonly used in ureteroscopic surgeries may cause in the long term in ureter. Methods: In this study, the animals were divided into 9 groups and according to their groups, ureters of the rabbits were endoscopically fitted with 2F and 3F ureter catheters. The catheters were left in place and withdrawn after a specified period of time. All the ureters were excised and evaluated macroscopically, microscopically and histologically. Ureter diameters were measured and FGF-2 (+) labeled fibroblasts were counted in connective tissue as stenosis precursors. Results: Macroscopically or microscopically, no stenosis was found in any group. The ureter diameter of the group that were catheterized for the longest time with the catheter that had the widest diameter was significantly lower than the group with the shorter duration and the catheter with the narrower diameter and the control group. When the groups were compared in terms of their FGF values, there was a significant difference in FGF-2 counts at all three ureter levels (p <0.05). Conclusion: The use of ureteral access sheath may lead to histological changes, as its diameter and duration increase.

Concomitant Hodgkin's lymphoma and gastric adenocarcinoma: a rare coincidence.

Gastric adenocarcinomas may be seen together with colon, prostate, breast, liver, lung and gynecological malignancies as synchronous or metachronous cancer. However, Hodgkin's lymphoma (HL) is rarely diagnosed with solid tumors. Herein, a 72-year-old man with both gastric adenocarcinoma and HL has been presented. Mass lesions far away from the primary tumor in cancer patients can be not only the sign of distant metastasis but also another primary malignancy. In the English literature, synchronous gastric adenocarcinoma and HL has been rarely reported, and as far as we know, this is the third case to be reported.