Adaptation of sea turtles to climate warming: Will phenological responses be sufficient to counteract changes in reproductive output?

Sea turtles are vulnerable to climate change since their reproductive output is influenced by incubating temperatures, with warmer temperatures causing lower hatching success and increased feminization of embryos. Their ability to cope with projected increases in ambient temperatures will depend on their capacity to adapt to shifts in climatic regimes. Here, we assessed the extent to which phenological shifts could mitigate impacts from increases in ambient temperatures (from 1.5 to 3°C in air temperatures and from 1.4 to 2.3°C in sea surface temperatures by 2100 at our sites) on four species of sea turtles, under a "middle of the road" scenario (SSP2-4.5). Sand temperatures at sea turtle nesting sites are projected to increase from 0.58 to 4.17°C by 2100 and expected shifts in nesting of 26-43 days earlier will not be sufficient to maintain current incubation temperatures at 7 (29%) of our sites, hatching success rates at 10 (42%) of our sites, with current trends in hatchling sex ratio being able to be maintained at half of the sites. We also calculated the phenological shifts that would be required (both backward for an earlier shift in nesting and forward for a later shift) to keep up with present-day incubation temperatures, hatching success rates, and sex ratios. The required shifts backward in nesting for incubation temperatures ranged from -20 to -191 days, whereas the required shifts forward ranged from +54 to +180 days. However, for half of the sites, no matter the shift the median incubation temperature will always be warmer than the 75th percentile of current ranges. Given that phenological shifts will not be able to ameliorate predicted changes in temperature, hatching success and sex ratio at most sites, turtles may need to use other adaptive responses and/or there is the need to enhance sea turtle resilience to climate warming.

Bilateral Krukenberg tumor in a 16-week pregnant woman.

The authors present the case of a G2P1001 who presented in 16-week gestation with bilateral Krukenberg tumor, abdominal pain, and iterative vomiting episodes. Although a few cases of Krukenberg tumor in pregnant women have been reported, no case reports asymptomatic and free of disease at 18 months were found in the English literature. Early detection followed by surgery and chemotherapy during pregnancy could possibly result in a favorable outcome in such patients.

Survival analysis of metastatic colorectal cancer patients who were treated with the five major therapeutic agents over the course of disease.

PURPOSE: Exposure to all active agents may be more important than specific sequence of drug administration in the treatment of patients with metastatic colorectal cancer (mCRC). The purpose of this study was to evaluate the overall survival (OS) of mCRC patients who were treated with all 5 major therapeutic agents used in this malignancy. METHODS: We retrospectively reviewed the medical records of 395 mCRC patients referred to our clinic. The study included patients who received 5-fluorouracil (5-FU)-, irinotecan- or oxaliplatin-based chemotherapy and at least 3 cycles of bevacizumab and 4 weeks of cetuximab sequentially in various combinations. RESULTS: Forty mCRC patients received the 5 major therapeutic agents effectively and sequentially, and their mean OS was 26.43±2.04 months. The 3- and 4- year OS survival rates were 26.7% and 16.7%, respectively. When survival analysis was limited to the metastatic patients with at least 6 cycles of bevacizumab therapy in addition to standard duration of other chemotherapeutic agents (N=33), the mean OS was 26.7±2.38 months. With a further survival analysis limited to metastatic patients who were treated with at least both 6 cycles of bevacizumab and 8 weeks of cetuximab in addition to other therapies (N=17), the mean OS was 44.8±11.03 months. CONCLUSION: This study demonstrated that in mCRC patients there may be a significant survival advantage if an adequate tumor response was achieved with all major therapeutic agents. Therefore, we believe that we should treat our patients with the 5 major therapeutic drugs as effectively as possible.

Evaluation of the efficacy of adjuvant chemotherapy in patients with high-risk stage II colon cancer.

PURPOSE: This study aimed at comparing the disease-free survival (DFS) in high-risk TNM stage II colon cancer patients who had been subjected to adjuvant chemotherapy and TNM low-risk stage II patients who did not receive chemotherapy. METHODS: We retrospectively reviewed the medical records of stage II colon cancer patients between January 2006 and December 2011. High-risk patients were defined those with any colonic obstruction/perforation, mucinous histology, inadequate lymph node sampling, T4 disease, lymphatic/ vascular or perineural invasion, preoperatively elevated carcinoembryonic antigen (CEA) and high-grade tumor. All patients with high-risk features received adjuvant chemotherapy. RESULTS: There were 42 patients in the high-risk treatment group and 21 patients in the non-treatment (observation) group. There were no significant differences in terms of gender, tumor size, tumor localization, or the number of excised lymph nodes between the groups. The median follow- up time was 33.9 months in the treatment group and 29.3 months in the non-treatment group. Recurrence developed in 4 patients (6.3%), 3 of which were in the treatment group. DFS in both groups was statistically similar. CONCLUSION: Adjuvant chemotherapy in the high-risk patients resulted in similar DFS as that in the low-risk patients. Although the role of adjuvant chemotherapy for stage II colon cancer is unclear, it is rational to offer adjuvant chemotherapy to patients with high-risk stage II colon cancer.

Apoptosis-mediated cytotoxic effects of ibandronic acid on hormone- and drug-refractory prostate cancer cells and human breast cancer cells.

Over 80% of patients with advanced breast and prostate cancer ultimately develop bone metastases. Ibandronic acid has proven efficacy for treatment of bone metastasis secondary to breast cancer. This study was designed to investigate the cytotoxic and apoptotic effects of ibandronic acid on hormone- and drug-refractory prostate carcinoma DU-145 and human breast cancer MCF-7 cell lines. Cytotoxicity was evaluated using an XTT cell proliferation kit, and apoptosis was assessed by enzyme-linked immunosorbent assay (histone-DNA fragmentation) and measurement of caspase 3/7 activity. With increasing concentrations of ibandronic acid there was a dose- and time-dependent decrease in cell numbers. MCF-7 cells were more resistant than DU-145 cells (half maximal inhibitory concentrations of 122 and 90 microM, respectively). Ibandronic acid induced apoptosis in both cell lines. The study showed an apoptosis-mediated cytotoxic effect for ibandronic acid (in addition to the already known osteoclast inhibiting effect) in breast cancer patients with bone metastases; which was also observed in prostate cancer cells. Further clinical studies involving breast and prostate cancer patients with bone metastases are warranted to confirm these findings.

The effect of racemic gossypol and at-101 on angiogenic profile of ovcar-3 cells: a preliminary molecular framework for gossypol enantiomers.

AIM: To compare the effect of racemic gossypol with its (-)/(-) enantiomer (AT-101) on expression profiles of angiogenic molecules by mRNA levels in human ovarian cancer cell line OVCAR-3. METHODS: Cell viability assay (2,3-bis (2-methoxy-4-nitro-5- sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) was used to detect cytotoxicity of gossypol enantiomers. DNA fragmentation by an enzyme-linked immunosorbent (ELISA) assay was used to evaluate the rate of apoptosis. The mRNA expression levels of angiogenic molecules were investigated by Human Angiogenesis RT2 ProfilerTM PCR Array (SuperArray, Frederick, MD). RESULTS: Both racemic form and AT-101 resulted in a significant cytotoxicity and induced apoptosis. This effect was observed in a dose- and time dependent manner. However, AT-101 was much more potent. In addition, the treatment of 10 microM of racemic gossypol alone and 3 microM of AT-101 alone resulted in significant down-regulation (>or= 3 fold) in mRNA levels of some pivotal angiogenic molecules in OVCAR-3, but altered gene profiles were different by the treatment of each enantiomer. CONCLUSION: The efficacy of two gossypol enantiomers in OVCAR-3 cells showed distinction. AT-101 was much more potent than racemic gossypol, not only by means of cell death and apoptosis, but also by modulation of angiogenic molecules released from OVCAR-3 cells. Further studies with endothelial cells should be done to verify the anti-angiogenic effect of gossypol enantiomers in cancer treatment.

Clinical significance and prognostic value of serum sHER-2/neu levels in patients with solid tumors.

The purpose of this study was to determine HER-2/neu in the serum of patients with solid tumors and to investigate its potential usefulness in predicting the clinical course of the disease. At the same time, we compared the ability of serum HER-2/neu, CA15.3, CA12-5, CA19-9, carcino embryonic antigen (CEA), and alpha-feto-protein (AFP) in breast, colorectal, and lung cancer patients. Forty, thirty-six, and twenty-three patients with lung, colon and breast cancer were included in this study, respectively. Serum levels of HER-2/neu, CA15.3, CA12-5, CA19-9, CEA, and AFP were measured. Her-2 neu levels were significantly higher in the breast cancer groups than colorectal and lung cancer and controls groups (P < 0.01). There is no significant difference when compared with others groups (P > 0.05). There was a positive correlation between the HER-2/neu and CA15-3 values in breast cancer groups. We found 0.75(0.59-0.90) for Her-2/neu from the area under the curve (AUC). P-value for breast cancer is 0.003, and we discovered that 9 ng/ml was the best inersection point. In this situation, we calculated that sensitivity was 65.2%, specificity was 100%, positive predictive value was 100%, negative predictive value 75.8%, and accuracy was 83.4%. These findings indicate that serum HER2/neu levels are clinically valuable in monitoring metastatic breast cancer and non-small cell lung cancer patients. Prognosis of breast cancer provides an additional value over the commonly used CA15-3 test. Measurements of levels of serum HER-2/neu provide prognostic and predictive information to the clinician and can especially be used for monitoring metastatic breast cancer patients. Further clinical validation is needed to confirm these findings.

Therapy, outcome and analysis of c-kit expression in patients with extrapulmonary small cell carcinoma.

In this study, we aimed to investigate the clinicopathological characteristics with special emphasis on c-kit expression and the treatment results of patients with extrapulmonary small cell carcinoma (EPSCC). The medical records of the patients with EPSCC were reviewed, and the data regarding patient and tumour characteristics, treatment and clinical outcome were retrieved and analysed. A total of 28 patients with the diagnosis of EPSCC were identified. There were 19 males and 9 females, with a mean age of 56.5 years. Patients with limited disease (LD) (n = 13) were treated with surgery, chemotherapy (CT) and radiotherapy with different sequences. Patients with extensive disease (ED) (n = 15) were mainly treated with combination CT. The median overall survival was 14.5 months in patients with LD compared to 11 months in those with ED (p = 0.029). Ten patients (36%) showed c-kit overexpression. There was no significant difference between the survival of c-kit-positive and c-kit-negative patients (p = 0.367). In conclusion, our study demonstrates that the prognosis of EPSCC is poor despite currently available treatments. C-kit may be considered as a potential target for novel therapeutical approaches.

Potential predictive factors for response to weekly paclitaxel treatment in patients with metastatic breast cancer.

The authors compare results obtained from weekly paclitaxel treatment in advanced breast cancer patients with biological and clinical prognostic factors. Expression of c-erbB-2, Ki-67, p53 and hormone receptors (HR) was examined by immunohistochemistry in samples of breast tissue from 30 patients. Univariate analysis showed that Ki-67 positivity and low performance status (PS) were associated with poor outcome (P <0.05). We observed that expression of p53 and c-erbB-2 did not have any negative effect on response to chemotherapy and survival. HR-negative patients had better response and slightly statistically significant overall survival (OS) rates compared to HR-positive patients (P >0.05). In a multivariate analysis low PS was the only significant predictor of shorter survival (P <0.05). In conclusion, while the expression of p53 and c-erbB-2 did not have any effect on treatment results, negative Ki-67 expression and negative HR status were associated with better OS in this patient population. PS was the only significant predictor for OS.

Predictive value of serum interleukin-8 levels in ovarian cancer patients treated with paclitaxel-containing regimens.

Previous findings showed that paclitaxel induces interleukin-8 (IL-8) transcription and secretion in ovarian cancer cells in vitro. We hypothesized that paclitaxel treatment, which is a standard care for ovarian cancer patients, may increase the secretion of IL-8, resulting in the elevated serum IL-8 levels. In this study, we investigated the relationship between paclitaxel exposure and IL-8 levels of an ovarian and a breast carcinoma cell line in vitro and serums of patients with ovarian carcinoma. Both MDAH 2774 ovarian and MCF-7 breast carcinoma cell lines were sensitive to paclitaxel-mediated cytotoxicity. However, supernatant levels of IL-8 assessed by enzyme-linked immunosorbent assay before and after treatment with different concentrations of paclitaxel were significantly lower in MCF-7 than in MDAH 2774. Serum IL-8 levels were measured in serum samples from patients with ovarian carcinoma before and after paclitaxel-containing treatment regimens. Forty-eight patients were included in the study. The basal level of IL-8 after paclitaxel-containing treatment was found to be significantly higher in the serums of patients who had high tumor burden than in patients who had optimal debulking surgery and low tumor burden. These data strongly suggest that IL-8 may be an important predictive marker for tumor volume as well as sensitivity to paclitaxel.

Arsenic trioxide-mediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines.

We studied the effect of arsenic trioxide (As2O3) on prostate and ovarian carcinoma cell lines. As2O3 has been shown to be effective in leukemia, and acute promyelocytic leukemia in particular, both in vitro and in vivo. As model cell lines, we used DU145 and PC-3 for prostate cancer and MDAH 2774 for ovarian cancer. New modalities of treatment are essential in these kinds of cancers, which produce a high death toll. The 3-(4,5-dimethyl-thiazoyl-2-yl)-2,5-diphenyl-tetrazolium bromide assay was used to evaluate cytotoxicity. Flow cytometric analysis and mono-oligo nucleosome detection-based ELISA were used to determine the apoptosis. Isobologram analysis was used to evaluate synergism and/or the additive effects of As2O3 and conventional chemotherapeutic agents. We clearly demonstrated that As2O3 has significant cytotoxic effect on both prostate and ovarian carcinoma cell lines. The dose range of As2O3 in all three cell lines was approximately 10(-6) M. The mechanism underlying cytotoxicity of As2O3 was shown to be apoptosis. The experiments by butylated hydroxyanisole showed that the cytotoxic effect of As2O3 was not through superoxide generation. There was no synergism, but the additive effects of As2O3 were demonstrated with cisplatin, adriamycin, and etoposide. We strongly suggest that As2O3 alone or in combination with conventional chemotherapeutic agents be evaluated further as a new agent for the treatment of prostate and ovarian cancers.