[Status and clinical response of fertility preservation in young patients with breast cancer].

Cancer treatments may improve the long-term survival rate of young patients with breast cancer, but also lead to a decrease in fertility. With the younger incidence of breast cancer in China, the fertility needs of this group have received more attention, and fertility preservation technology suitable for cancer patients is developing continuously. However, there are still many problems in the implementation of fertility preservation for young breast cancer patients in China. Patients and breast surgeons have insufficient understanding and conservative attitudes towards fertility preservation technology. And there is a lack of reproductive experts in the treatment process. What's more, the long-term follow-up and information management of patients undergoing fertility preservation are defective. In response to the above, this paper discusses how to deal with patients with potential reproductive needs in clinical practice from the perspective of breast surgeons. The first is to improve their own understanding of fertility preservation, such as the progress of relevant technologies and applicable population, when to intervene, when and how to get pregnant after cancer treatment. Secondly, education for patients must be strengthened, which should include not only fertility preservation, but also scientific contraceptive methods during cancer treatment and treatment measures for unexpected pregnancy. Finally, hospitals and relevant units should standardize the multidisciplinary team of breast cancer, and strengthen the comprehensive management of young breast cancer patients, thus to provide young breast cancer patients with more scientific cancer treatment programs and more reproductive opportunities.

[Multidisciplinary cooperation strengthens individualized management of breast cancer in pregnancy].

As the pregnant patient with breast cancer is in a special physiological period, both the efficacy of mother and the safety of developing fetus should be considered during the whole process of diagnosis and treatment. It is particularly important for multidisciplinary teams including breast, obstetrics and nursing departments to make a secure and effective individualized plan for those in different gestational week and different stages of breast cancer development. Pregnancy risk assessment and whole-process multidisciplinary case management mode for breast cancer during pregnancy are helpful for the early detection of abnormal health status of pregnant women and fetuses, enabling rapid and efficient treatment, reducing the occurrence of adverse medical events, and maximizing the safety of pregnant women and fetuses. Obstetricians should pay attention to the chief complaints of pregnant women and conduct regular breast ultrasound examinations. Once anything suspicious is found, breast surgeons need to take charge of a multidisciplinary discussion. Not only should the multidisciplinary collaborative outpatient clinic determine the treatment plan for breast cancer during pregnancy, but also the concept of multidisciplinary collaboration should be incorporated into the follow-up treatment process, including active surgical treatment, selection of neoadjuvant chemotherapy and adjuvant chemotherapy, avoidance of endocrine therapy, targeted therapy and radiotherapy, and adherence to multidisciplinary follow-up, etc. Multidisciplinary case management of breast cancer during pregnancy is necessary and feasible, and more prospective clinical studies need to be carried out to help improve clinical diagnosis and treatment strategies.

[Characteristics on spatial and temporal distribution as well as the driving effect of meteorological factors on brucellosis in Datong city, Shanxi province, 2005-2015].

Objective: To explore the spatio-temporal epidemic trends and related driving effects of meteorological factors on brucellosis in Datong city, Shanxi province, from 2005 to 2015. Methods: We collected the surveillance data on brucellosis and related meteorological data in Datong city from 2005 to 2015, to describe the epidemic characteristics of the disease. Quasi-Poisson distribution lag non-liner model (DLNM) was built to explore the driving effect of monthly meteorological data on the disease. Results: From 2005 to 2015, Datong city reported a total of 17 311 cases of brucellosis including one death, with the annual average incidence as 47.43 per 100 000 persons. A rising trend was seen during the study period. The monthly incidence of Brucellosis presented an obvious curve with a major peak from March to June, accounted for 48.40% of the total cases. The high incidence areas in the city gradually expanded from the northeast and southeast to the western areas. Results from the DLNM studies suggested that seasonality of brucellosis in Datong was significantly affected by metrological factors such as evaporation, rainfall and temperature. The peak of delayed effect appeared the highest when the monthly cumulative evaporation capacity was 140-260 mm and the monthly cumulative rainfall was 20-60 mm with lag less than 1 month or the monthly temperature was -13 ℃ with lag of 4-5 months. Conclusions: The incidence of human brucellosis in Datong city increased significantly from 2005 to 2015. Meteorological factors such as evaporation, rainfall, temperature all showed significant driving effects on the disease.

[Association between serum lipid level and depression in patients with chronic heart failure].

Objective: To investigate the association between serum lipid level and depression in patients with chronic heart failure (CHF). Methods: A total of 348 patients with CHF from the First department of Cardiology of the people's hospital of Shaanxi province from September 2016 to June 2017 were included.The Hamilton Depression Scale (HAMD) was used to evaluate the degree of depression and some related clinical data were tested.The serum lipid level and depression scores in the patients were analyzed using Pearson correlation analysis, and Logistic regression analysis was used to analyze the confounding factors of depression. Results: There was significant difference in the proportion of depression between normal serum lipid group and dyslipidemia group (P=0.044). Pearson correlation analysis showed that depression score was linearly related to total cholesterol (r=0.326, P<0.001) and low density lipoprotein cholesterol (r=0.354, P<0.001), and Logistic regression analysis showed that after adjusting for age, BMI, triglyceride, low density lipoprotein cholesterol, creatinine, total bilirubin, albumin, B type natriuretic peptide, total cholesterol (OR=3.523, P=0.007) and high density lipoprotein cholesterol (OR=0.205, P=0.041) were associated with depression in CHF patients. Conclusion: Total cholesterol can increase the risk of depression, and high density lipoprotein cholesterol can reduce the risk of depression in CHF patients.

Sudden-onset unilateral ptosis induced by pituitary Macroadenoma, with false-positive jolly and neostigmine tests.

The development of ptosis as a consequence of pituitary tumor is an exceptionally rare occurrence. Here, we describe the case of sudden-onset unilateral ptosis induced by pituitary macroadenoma. The condition was characterized by false-positive Jolly and neostigmine tests. These findings mimic oculomotor nerve palsy and make the correct diagnostics rather challenging. The case points to the fact that patients with acquired ptosis need detailed neuroophthalmological examination.

[Thoughts on optimizing the breast cancer screening strategies and implementation effects].

Reasonable and effective breast cancer screening can make early diagnosis of breast cancer, improve the cure rate, prolong survival and improve the patients' quality of life. China has made preliminary exploration and attempt in breast cancer screening, however, there are still some problems that have not been solved in terms of the proportion of opportunistic screening, the selection of screening targets, methods and frequency, and the judgment of screening results. Therefore, this article analyzes the above problems in details, and presents some thoughts and recommendations on how to optimize the breast cancer screening strategies and implementation effects in China, from the experience of clinical practice, under the background of constantly emerging new research results and techniques and the rapid development of artificial intelligence, that is, to adjust measures to local conditions, provide personalized strategies, achieve precise screening, preach and educate, ensure health insurance coverage, improve quality control, offer technical support and employ artificial intelligence.

[Retrospective analysis of diagnosis and treatment of breast cancer in pregnancy].

Objective: To investigate the principles of diagnosis and treatment of breast cancer during pregnancy. Methods: Clinical data of patients with breast cancer during pregnancy admitted to Obstetrics and Gynecology Hospital of Fudan University between January 2012 to July 2017 were analyzed retrospectively. A total of 17 patients were diagnosed with breast cancer in pregnancy, the median age was 32 years (range from 25 to 45 years old), pathological staging revealed 2 patient with stage 0, 1 with stage Ⅱa, 7 with stage Ⅱb, 1 with stage Ⅲa, 2 with stage Ⅲc, 4 with stage Ⅳ. Results: Thirteen patients received surgical treatment in pregnancy, the gestational age at surgery was (27.7±4.6) weeks; 2 patients with ductal carcinoma in situ received mastectomy, 11 patients with breast cancer underwent modified radical mastectomy. In patients undergoing surgery during pregnancy, no prophylactic contractions were used in 4 patients who had been treated earlier, there were 2 patients with frequent contractions within 24 hours after operation in these patients. Follow-up 9 patients were given oral nifedipine to prevent contractions, no obvious contractions occurred after the operation. Seven patients received chemotherapy during pregnancy; the chemotherapy of 4 cases of triple negative breast cancer was weekly paclitaxel sequential epirubicin and cyclophosphamide, the chemotherapy of the other three patients was docetaxel sequential epirubicin and cyclophosphamide. Fifteen patients underwent cesarean section to terminate pregnancy, 2 patients underwent spontaneous labor. The gestational age of birth was (36.9 ±1.3) weeks. Less than 35 weeks of termination of pregnancy occurred in one patient, the fetus was delivered to the neonatal intensive care unit due to neonatal respiratory distress syndrome, and suffered from congenital dysaudia. The prognosis of the other 16 survived infants was good. The median follow-up time was 10 months (range from 4 to 27) months, in 13 patients of stage 0 to Ⅲc, one patient were diagnosed with bone metastasis at 12 months after surgery, the remaining 12 patients had no disease progression, the progression free survival rate was 12/13, the overall survival rate was 13/13. Among the 4 patients with stage Ⅳ, one died in 7 months after delivery, one had new liver metastasis in 8 months after delivery. The remaining 2 patients were in stable condition. Conclusions: Breast cancer in pregnancy can be treated effectively, multidisciplinary cooperation and detailed assessment of maternal-fetal risks and benefits are necessary. Chemotherapy during pregnancy is safe for maternal-fetal, but it needed a large sample of clinical studies and long-term follow-up. The neonatal outcome was associated with gestational age, and therefore premature delivery was avoided as much as possible during treatment.

Thrombin Activates Latent TGFß1 via Integrin αvß1 in Gingival Fibroblasts.

Transforming growth factor ß (TGFß) regulates cell proliferation, differentiation, migration, apoptosis, and extracellular matrix production. It also plays a pivotal role in the pathogenesis of gingival overgrowth. Thrombin is a key player in tissue repair, remodeling, and fibrosis after an injury, and it exerts profibrotic effects by activating protease-activated receptors. Connective tissue growth factor (CTGF or CCN2) modulates cell adhesion, migration, proliferation, matrix production, and wound healing. It is overexpressed in many fibrotic disorders, including gingival overgrowth, and it is positively associated with the degree of fibrosis in gingival overgrowth. In human gingival fibroblasts, we previously found that TGFß1 induced CCN2 protein synthesis through c-jun N-terminal kinase and Smad3 activation. Thrombin stimulates CCN2 synthesis through protease-activated receptor 1 and c-jun N-terminal kinase signaling. Curcumin inhibited TGFß1- and thrombin-induced CCN2 synthesis. In this study, we demonstrated that thrombin and protease-activated receptor 1 agonist SFLLRN induced latent TGFß1 activation and Smad3 phosphorylation in human gingival fibroblasts. Pretreatment with a TGFß-neutralizing antibody, TGFß type I receptor inhibitor SB431542, and Smad3 inhibitor SIS3 inhibited approximately 86%, 94%, and 100% of thrombin-induced CCN2 synthesis, respectively. Furthermore, blocking integrin subunits αv and ß1 with antibodies effectively inhibited SFLLRN-induced Smad3 phosphorylation and CCN2 synthesis and increased activated TGFß1 levels; however, similar effects were not observed for integrins αvß3 and αvß5. These results suggest that protease-activated receptor 1-induced CCN2 synthesis in human gingival fibroblasts is mediated through integrin αvß1-induced latent TGFß1 activation and subsequent TGFß1 signaling. Moreover, curcumin dose dependently decreased thrombin-induced activated TGFß1 levels. Curcumin-inhibited thrombin-induced CCN2 synthesis in human gingival fibroblasts is caused by the suppression of latent TGFß1 activation.

Performance and Mix Measurements of Indirect Drive Cu-Doped Be Implosions.

The ablator couples energy between the driver and fusion fuel in inertial confinement fusion (ICF). Because of its low opacity, high solid density, and material properties, beryllium has long been considered an ideal ablator for ICF ignition experiments at the National Ignition Facility. We report here the first indirect drive Be implosions driven with shaped laser pulses and diagnosed with fusion yield at the OMEGA laser. The results show good performance with an average DD neutron yield of ∼2×10^{9} at a convergence ratio of R_{0}/R∼10 and little impact due to the growth of hydrodynamic instabilities and mix. In addition, the effect of adding an inner liner of W between the Be and DD is demonstrated.

NADPH Oxidase 4 Mediates TGFß1-induced CCN2 in Gingival Fibroblasts.

Transforming growth factor ß (TGFß) plays a central role in the pathogenesis of gingival overgrowth (GO). Connective tissue growth factor (CTGF; or CCN2) is induced by TGFß in human gingival fibroblasts (HGFs) and is overexpressed in GO tissues. CCN2 creates an environment favorable for fibrogenesis and is required for the maximal profibrotic effects of TGFß. We previously showed that Src, JNK, and Smad3 mediate TGFß1-induced CCN2 protein expression in HGFs. Moreover, Src is an upstream signaling transducer of JNK and Smad3. Recent studies suggested that NADPH oxidase (NOX)-dependent redox mechanisms are involved in mediating the profibrotic effects of TGFß. In this study, we demonstrated that TGFß1 upregulated NOX4 protein expression and increased reactive oxygen species (ROS) production in HGFs. Genetic or pharmacologic targeting of NOX4 abrogated TGFß1-induced ROS production; Src, JNK, and Smad3 activation; and CCN2 and type I collagen protein expression in HGFs. Our results indicated that NOX4-derived ROS play pivotal roles in activating Src kinase activity leading to the activation of canonical (Smad3) and noncanonical (JNK) cascades that cooperate to attain maximum CCN2 expression. Furthermore, we demonstrated that curcumin significantly inhibited the TGFß1-induced NOX4 protein expression in HGFs. Curcumin potentially qualifies as an agent to control GO by suppressing TGFß1-induced NOX4 expression in HGFs.

Towards stable silicon nanoarray hybrid solar cells.

Silicon nanoarray hybrid solar cells benefit from the ease of fabrication and the cost-effectiveness of the hybrid structure, and represent a new research focus towards the utilization of solar energy. However, hybrid solar cells composed of both inorganic and organic components suffer from the notorious stability issue, which has to be tackled before the hybrid solar cells could become a viable alternative for harvesting solar energy. Here we show that Si nanoarray/PEDOT:PSS hybrid solar cells with improved stability can be fabricated via eliminating the water inclusion in the initial formation of the heterojunction between Si nanoarray and PEDOT:PSS. The Si nanoarray hybrid solar cells are stable against rapid degradation in the atmosphere environment for several months without encapsulation. This finding paves the way towards the real-world applications of Si nanoarray hybrid solar cells.

FOXM1 targets NBS1 to regulate DNA damage-induced senescence and epirubicin resistance.

FOXM1 is implicated in genotoxic drug resistance but its mechanism of action remains elusive. We show here that FOXM1-depletion can sensitize breast cancer cells and mouse embryonic fibroblasts (MEFs) into entering epirubicin-induced senescence, with the loss of long-term cell proliferation ability, the accumulation of γH2AX foci, and the induction of senescence-associated ß-galactosidase activity and cell morphology. Conversely, reconstitution of FOXM1 in FOXM1-deficient MEFs alleviates the accumulation of senescence-associated γH2AX foci. We also demonstrate that FOXM1 regulates NBS1 at the transcriptional level through an forkhead response element on its promoter. Like FOXM1, NBS1 is overexpressed in the epirubicin-resistant MCF-7Epi(R) cells and its expression level is low but inducible by epirubicin in MCF-7 cells. Consistently, overexpression of FOXM1 augmented and FOXM1 depletion reduced NBS1 expression and epirubicin-induced ataxia-telangiectasia mutated (ATM)phosphorylation in breast cancer cells. Together these findings suggest that FOXM1 increases NBS1 expression and ATM phosphorylation, possibly through increasing the levels of the MRN(MRE11/RAD50/NBS1) complex. Consistent with this idea, the loss of P-ATM induction by epirubicin in the NBS1-deficient NBS1-LBI fibroblasts can be rescued by NBS1 reconstitution. Resembling FOXM1, NBS1 depletion also rendered MCF-7 and MCF-7Epi(R) cells more sensitive to epirubicin-induced cellular senescence. In agreement, the DNA repair-defective and senescence phenotypes in FOXM1-deficent cells can be effectively rescued by overexpression of NBS1. Moreover, overexpression of NBS1 and FOXM1 similarly enhanced and their depletion downregulated homologous recombination (HR) DNA repair activity. Crucially, overexpression of FOXM1 failed to augment HR activity in the background of NBS1 depletion, demonstrating that NBS1 is indispensable for the HR function of FOXM1. The physiological relevance of the regulation of NBS1 expression by FOXM1 is further underscored by the strong and significant correlation between nuclear FOXM1 and total NBS1 expression in breast cancer patient samples, further suggesting that NBS1 as a key FOXM1 target gene involved in DNA damage response, genotoxic drug resistance and DNA damage-induced senescence.

Whole-genome duplications contributed to the expansion of cytochrome b5 genes in Paramecium tetraurelia.

Cytochrome b5 (cyt b5) genes encode ubiquitous electron transport hemoproteins found in animals, plants, fungi, and purple bacteria. However, little is known about their evolutionary history in genomes so far. Here, we conducted an extensive genome-wide survey of cyt b5 genes in 20 representative model species and identified 310 of these genes. Both the absolute number and relative proportion of cyt b5 genes in Paramecium tetraurelia were significantly higher than those in other genomes. Our data also showed that whole-genome duplications (WGDs), especially the recent WGD, contributed to the species-specific expansion of cyt b5 genes in the Paramecium genome. Furthermore, 24 cyt b5 genes were identified as the minimal number of ancestral cyt b5 in the ancestral Paramecium genome, which is also the largest number of these genes encountered in an organism. These results suggest that an excess of cyt b5 genes were selectively retained in this species even before the three WGDs took place. Although more cyt b5 genes were retained in P. tetraurelia than in other genomes, more cyt b5 losses were also observed in the P. tetraurelia genome, suggesting that the balance of gene retention and loss maintained an optimum dosage of cyt b5 genes.

Protein adsorption and peroxidation of rat retinas under stimulation of a neural probe coated with polyaniline.

For the purpose of investigating the potential use of conducting polymers, i.e. polyaniline (PANi), as electrode coating material for improving the function of neural probes, a PANi-coated platinum (Pt) electrode was prepared by the in situ polymerization method. Protein adsorption was observed by atomic force microscopy/scanning electron microscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis, as well as quantification. Peroxidation of rat retinas was evaluated by determination of conjugated dienes and PLOOH, which were quantified by UV-visible spectrophotometer and high-performance liquid chromatography. The stability of PANi coating for 6 months was also estimated with an in vitro electrical stimulation system. This revealed that: (1) PANi with regular and compact nanoparticles 20-40 nm in diameter was successfully polymerized on the uncoated platinum electrode surface; (2) the PANi-coated Pt electrode adsorbed fewer retinal fragments and induced less peroxidation than the uncoated platinum electrode; (3) in contrast to the uncoated platinum electrode, the PANi-coated Pt electrode surface tended to aggregate retinal fragments rather than spread them, which may help to reduce inflammation and scar formation in long-term implantation; (4) the PANi coating exhibited excellent properties in terms of the intactness and the stable nanoparticle morphology after 6 months' electrical stimulation, while corrosion occurred on the uncoated platinum electrode after 1 month.

Current research of C-Sight visual prosthesis for the blind.

Electrical stimulation of the optic nerve with penetrating electrode array for visual recovery had been proposed by C-Sight group. This paper presents the latest progress of various component parts of visual prosthesis, including design and testing of neural stimulator, fabrication of multi-channel flexible microelectrode array. According to the experiment data, the linearity between practical stimulator output and the setting parameters has been validated. The temporal properties of EEP evoked by optic nerve stimulation with penetrating electrodes will be introduced briefly according to in vivo electrophysiological study.

Loss of type III transforming growth factor-beta receptor expression is due to methylation silencing of the transcription factor GATA3 in renal cell carcinoma.

Loss of transforming growth factor-beta receptor III (TbetaRIII) correlates with loss of transforming growth factor-beta (TGF-beta) responsiveness and suggests a role for dysregulated TGF-beta signaling in clear cell renal cell carcinoma (ccRCC) progression and metastasis. Here we identify that for all stages of ccRCC TbetaRIII expression is downregulated in patient-matched tissue samples and cell lines. We find that this loss of expression is not due to methylation of the gene and we define GATA3 as the first transcriptional factor to positively regulate TbetaRIII expression in human cells. We localize GATA3's binding to a 10-bp region of the TbetaRIII proximal promoter. We demonstrate that GATA3 mRNA is downregulated in all stages, of ccRCC, mechanistically show that GATA3 is methylated in ccRCC patient tumor tissues as well as cell lines, and that inhibiting GATA3 expression in normal renal epithelial cells downregulates TbetaRIII mRNA and protein expression. These data support a sequential model whereby loss of GATA3 expression through epigenetic silencing decreases TbetaRIII expression during ccRCC progression.

Prognostic significance of hypoxia-inducible factor-1alpha, TWIST1 and Snail expression in resectable non-small cell lung cancer.

BACKGROUND: Metastasis is the most common cause of disease failure and mortality for non-small cell lung cancer (NSCLC) after surgical resection. Snail and TWIST1 are epithelial-mesenchymal transition (EMT) regulators which induce metastasis. Intratumoral hypoxia followed by stabilisation of hypoxia-inducible factor 1alpha (HIF-1alpha) promotes metastasis through regulation of certain EMT regulators. The aim of this study was to evaluate the prognostic value of HIF-1alpha, TWIST1 and Snail expression in patients with resectable NSCLC. METHODS: A retrospective analysis of 87 patients with resectable NSCLC from Taipei Veterans General Hospital between 2003 and 2004 was performed using immunohistochemistry to analyse HIF-1alpha, TWIST1 and Snail expression. The association between HIF-1alpha, TWIST1 and Snail expression and patients' overall and recurrence-free survivals was investigated. RESULTS: Overexpression of HIF-1alpha, TWIST1 or Snail was shown in 32.2%, 36.8% and 55.2% of primary tumours, respectively. Overexpression of HIF-1alpha, TWIST1 or Snail in primary NSCLCs was associated with a shorter overall survival (p = 0.005, p = 0.026, p = 0.009, respectively), and overexpression of HIF-1alpha was associated with a shorter recurrence-free survival (p = 0.016). We categorised the patients into four groups according to the positivity of HIF-1alpha/TWIST1/Snail to investigate the accumulated effects of these markers on survival. Co-expression of more than two markers was an independent prognostic indicator for both recurrence-free survival and overall survival (p = 0.004 and p<0.001, respectively, by multivariate Cox proportional hazards model). CONCLUSIONS: Co-expression of more than two markers from HIF-1alpha, TWIST1 and Snail is a significant prognostic predictor in patients with NSCLC.

Peptides enhance magnesium signature in calcite: insights into origins of vital effects.

Studies relating the magnesium (Mg) content of calcified skeletons to temperature often report unexplained deviations from the signature expected for inorganically grown calcite. These "vital effects" are believed to have biological origins, but mechanistic bases for measured offsets remain unclear. We show that a simple hydrophilic peptide, with the same carboxyl-rich character as that of macromolecules isolated from sites of calcification, increases calcite Mg content by up to 3 mole percent. Comparisons to previous studies correlating Mg content of carbonate minerals with temperature show that the Mg enhancement due to peptides results in offsets equivalent to 7 degrees to 14 degrees C. The insights also provide a physical basis for anecdotal evidence that organic chemistry modulates the mineralization of inorganic carbonates and suggest an approach to tuning impurity levels in controlled materials synthesis.

FLJ10540-elicited cell transformation is through the activation of PI3-kinase/AKT pathway.

A significant challenge in the post-genomic era is how to prioritize differentially expressed and uncharacterized novel genes found in hepatocellular carcinoma (HCC) microarray profiling. One such category is cell cycle regulated genes that have only evolved in higher organisms but not in lower eukaryotic cells. Characterization of these genes may reveal some novel human cancer-specific abnormalities. A novel transcript, FLJ10540 was identified. FLJ10540 is overexpressed in HCC as examined by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. The patients with higher FLJ10540 expression had a poor survival than those with lower FLJ10540 expression. Functional characterization indicates that FLJ10540 displays a number of characteristics associated with an oncogene, including anchorage-independent growth, enhanced cell growth at low serum levels and induction of tumorigenesis in nude mice. FLJ10540-elicited cell transformation is mediated by activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway. Moreover, FLJ10540 forms a complex with PI3K and can activate PI3K activity, which provides a mechanistic basis for FLJ10540-mediated oncogenesis. Together, using a combination of bioinformatics searches and empirical data, we have identified a novel oncogene, FLJ10540, which is conserved only in higher organisms. The finding raises the possibility that FLJ10540 is a potential new therapeutic target for HCC treatment. These findings may contribute to the development of new therapeutic strategies that are able to block the PI3K/AKT pathway in cancer cells.