TTTY15 knockdown could significantly reduce the proliferation, migration and invasion of ESCC cells, and miR-337-3p mimics had similar effects. In addition, overexpression of TTTY15 inhibited miR-337-3p by binding with it. TTTY15 could indirectly modulate JAK2, and overexpression of TTTY15 could reverse the inhibitory effects of miR-337-3p on malignant phenotypes of ESCC cells. In conclusion, TTTY15 plays an oncogenic role in ESCC by targeting miR-337-3p/JAK2 axis.Malignant melanoma is a kind of highly invasive and deadly diseases. The BRAF inhibitor (BRAFi) such as vemurafenib could achieve a high response rate in melanoma patients with BRAF mutation. However, melanoma cells could easily develop resistance as well as addiction to BRAFi. Based on the drug addiction, intermittent treatment has been proposed to select against BRAFi-resistant melanoma cells. Because different dosages of BRAFi might be used in patients, it is necessary to know about the relationship between drug dosage and the degree of addiction. To address the problem, four drug-resistant melanoma cell sublines (A375/R0.5, A375/R2.0, M14/R0.5 and M14/R2.0) were established by continuously exposure of melanoma A375 or M14 cells to 0.5 or 2.0 μM vemurafenib. Vemurafenib withdrawal resulted in much stronger suppression on clone formation in A375/R2.0 and M14/R2.0, compared with A375/R0.5 and M14/R0.5, respectively. Meanwhile, stronger upregulation of ERK1/2-FRA-1 pathway could be observed in A375/R2.0 and M14/R2.0. Further detection showed that some proinflammatory cytokines downstream of ERK1/2-FRA-1 pathway were upregulated after drug withdrawal, and the conditioned medium collected from the resistant A375 cells could inhibit clone formation. Furthermore, vemurafenib withdrawal resulted in suppressed cell proliferation rather than cell senescence, with stronger effect on A375/R2.0 compared with A375/R0.5. This study suggested that the depth of vemurafenib addiction in resistant melanoma cells is positively correlated to the drug dosage, which might be underpinned by the ERK1/2-FRA-1 pathway and the related cytokines.Inflammatory myofibroblastic tumour (IMT) is a rare malignancy with limited responses to corticosteroids and chemotherapy. About half of cases have activating rearrangements in the ALK gene which could be targeted with ALK inhibitors. A 40-year-old man presented with a large right lung mass and nodal, trapezius and cerebral metastases. Biopsy confirmed IMT with TPM4-ALK fusion. He was treated with prednisolone without clinical benefit. He received the Trk/ROS1/ALK inhibitor entrectinib in a clinical trial but his disease progressed in less than 3 months. Ifosfamide and etoposide in addition to radiotherapy to the brain and chest were administered. Transient improvement in the radiotherapy-treated areas was observed but his disease progressed shortly afterwards on all sites including the development of new adrenal metastasis. Compassionate use of the third-generation ALK inhibitor lorlatinib resulted in excellent partial response on all disease sites after 2 months, followed by a further 6 months of disease stabilisation. Repeat imaging showed slight increase in size of the cerebral metastasis but stable disease elsewhere, for which he was given stereotactic radiotherapy. His disease progressed 3 months later and lorlatinib was substituted with another ALK inhibitor brigatinib but he deteriorated and died shortly afterwards. Our patient tolerated lorlatinib well for 11 months with minimal toxicities, although he developed unilateral right-sided lung consolidation that was probably related to a combination of infection, radiotherapy and lorlatinib, which needed treatment with antibiotics and corticosteroids. This case demonstrates a role of lorlatinib in the treatment of TPM4-ALK-rearranged IMT despite failure of entrectinib.Anaplastic lymphoma kinase (ALK)-translocations are present in up to 5% of non-small cell lung cancer (NSCLC), most of them being adenocarcinomas. Even though the availability of five potent ALK-inhibitors for the treatment of ALK-positive NSCLC patients, there is no consensus about the ideal therapy sequence. Alectinib has been so far successfully and routinely used as first-line therapy, especially in patients presenting central nervous system lesions; however, with the very recent European approval of brigatinib in the first line, a new treatment option is now available for ALK+ patient collective. In this case series, efficient systemic and intracranial responses to alectinib late-line treatment following brigatinib therapy are reported. This therapeutic sequence is going to gain therefore more importance in a near future.Tumor human epidermal growth factor receptor 2 (HER2) status is defined by either protein expression using immunohistochemistry (IHC) or gene amplification using fluorescence in situ hybridization (FISH). Approximately 20% of HER2-positive breast cancer is HER2 IHC 2+/FISH-positive. Unlike trastuzumab, it has not been studied whether the response to trastuzumab emtansine (T-DM1) differs according to HER2-positive status. We retrospectively identified and reviewed medical records of all patients with HER2-positive advanced breast cancer (ABC) who received T-DM1 in our hospital from October 2013 to December 2016. We compared the objective response rate (ORR) and progression-free survival (PFS) between patients in the HER2 IHC 3+ group and those in the HER2 IHC 2+/FISH-positive group. A total of 39 patients (IHC 3+ n = 32; IHC 2+/FISH-positive n = 7) were analyzed. Nineteen (48.7%), 13 (33.3%), and 29 (74.4%) patients had received at least one prior chemotherapy, more than three lines of chemotherapy, and prior pertuzumab for ABC, respectively. ORR was significantly higher in the IHC 3+ group than in the IHC 2+/FISH-positive group (53.3% vs. 0%, P = 0.024). Median PFS was 7.9 months in the IHC 3+ group versus 3.9 months in the IHC 2+/FISH-positive group (hazard ratio 0.68; 95% confidence interval 0.28-1.69, P = 0.408). Among the HER2-positive ABC patients treated with T-DM1, ORR was significantly worse in HER2 IHC 2+/FISH-positive than in HER2 IHC 3+ patients. Median PFS tended to be shorter in patients with HER2 IHC 2+/FISH-positive.In the past few years, the immune checkpoint inhibitor (ICI) nivolumab has become standard of care in the treatment of metastatic renal cell carcinoma (mRCC) progressing after antiangiogenic agents. To date, neither expression of programmed death ligand-1 (PD-L1) nor any other biomarker can be used to predict responses to ICIs, although intermediate-poor International Metastatic Database of Renal Carcinoma (IMDC) risk patients and those with sarcomatoid tumors appear to achieve superior benefit from immunotherapy. Paradoxically, ICIs may sometimes increase the speed of tumor growth. This rare phenomenon, called hyperprogression, has first been described in patients with melanoma and lung cancer treated with ICIs and is associated with poor survival. Here, we present the case of a patient affected by an intermediate IMDC risk mRCC with diffuse sarcomatoid features who achieved long disease control with first-line sunitinib and then started a second-line treatment with nivolumab. Unexpectedly, he experienced a dramatic acceleration of tumor growth and died soon after the third infusion of nivolumab. Then, we review the frequency of hyperprogression in mRCC and discuss the biological peculiarity of sarcomatoid RCC in terms of different responses to ICIs and antiangiogenic agents.

Available data indicate that patients with primary aldosteronism have an increased risk of cardiovascular events and cardiovascular risk seems to be, at least in part, independent of blood pressure (BP) values. Patients with primary aldosteronism have a greater prevalence of left ventricular (LV) hypertrophy and subtle alterations of ventricular function, which might contribute to the increase in cardiovascular risk. Recently, a noninvasive approach for the estimation of LV mechanical efficiency, obtained by echocardiography has been proposed.

To evaluate the determinants of myocardial mechanoenergetic efficiency index (MEEi), in a large group of patients with primary aldosteronism (n = 99) and in a control group of essential hypertensive patients (n = 99) matched for age, sex and BP values.

No differences between groups for age, sex, BMI, BP values, glucose, lipid profile and renal function were observed. LV mass index was greater in primary aldosteronism vs. essential hypertensive patients (46.0 ± 16.n the myocardium, which could lead to the occurrence of cardiovascular complications and therefore these findings may contribute to explain the increased risk of cardiovascular events in patients with primary aldosteronism.

In patients with primary aldosteronism myocardial MEEi is lower as compared with essential hypertensive patients. A reduced MEEi may reflect an impairment of production and utilization of energy in the myocardium, which could lead to the occurrence of cardiovascular complications and therefore these findings may contribute to explain the increased risk of cardiovascular events in patients with primary aldosteronism.

The role of adrenal venous sampling (AVS) has been challenged by some recent evidence. This study aimed to compare the role of AVS and computed tomography (CT) in the management of primary aldosteronism.

Patients who underwent unilateral adrenalectomy for primary aldosteronism at a single center between January 2015 and December 2018 were included, and postoperative outcomes of the patients who underwent surgery based on CT (n = 195) or AVS (n = 40) were compared. The data of all the patients who underwent AVS successfully (n = 75) during this period were also collected and analyzed.

There were no significant differences between the CT-guided and AVS-guided adrenalectomies in most of the postoperative outcomes, and the proportion of patients achieving cure of hypokalemia (CT vs. AVS, 98.3 vs. 96.4%) and alleviation of hypertension (89.2 vs. 92.9%) were similar between the two groups. However, since the baseline characteristics of the two groups were not identical, the AVS-guided group showed greater improvement in postoperative hypokalemia and greater reduction in the number of antihypertensive medications than the CT-guided group. In addition, for the 75 patients who underwent AVS successfully, the concordance rate between CT abnormalities and AVS lateralization was 60.0% in total, and 22.7% patients changed treatment plans according to the AVS results.

Although the clinical outcomes were not significantly different between the CT-guided and AVS-guided group, the AVS-guided group seemed to benefit more from the surgery, and a considerable number of patients with primary aldosteronism would have received inappropriate treatment if they did not undergo AVS.

Although the clinical outcomes were not significantly different between the CT-guided and AVS-guided group, the AVS-guided group seemed to benefit more from the surgery, and a considerable number of patients with primary aldosteronism would have received inappropriate treatment if they did not undergo AVS.

Age-related increases in systemic blood flow [stroke volume (SV), cardiac output (CO), and aortic flow (Q)] contribute substantially to untreated or inadequately controlled (uncontrolled) blood pressure (BP) in Africa. We aimed to identify the haemodynamic determinants of uncontrolled systolic–diastolic (Syst–diast HT) versus uncontrolled isolated systolic (ISH) or diastolic (IDH) hypertension.

Using central arterial pressure and aortic outflow tract velocity and diameter measurements (echocardiography), the haemodynamic correlates of BP were determined in 725 community participants of African ancestry (19.6% uncontrolled Syst–diast HT, 9.2% uncontrolled ISH, 11.3% uncontrolled IDH).

Independent of confounders, compared with those with a normotensive BP, those with uncontrolled Syst–diast HT had increases in SV, CO, Q, systemic vascular resistance (SVR) and aortic characteristic impedance (Zc) and decreases in total arterial compliance (TAC) (P < 0.05–P < 0.0001). In multivariate regression models, uncontrolled Syst–diast HT was as strongly associated with Q, SV or CO as with SVR (P = 0.