Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance

Cancer development is a multistep process in which cells must overcome a series of obstacles before they can become fully developed tumors. First, cells must develop the ability to proliferate unchecked. Once this is accomplished, they must be able to invade the neighboring tissue, as well as provide themselves with oxygen and nutrients. Finally, they must acquire the ability to detach from the newly formed mass in order to spread to other tissues, all the while evading an immune system that is primed for their destruction. Furthermore, increased levels of inflammation have been shown to be linked to the development of cancer, with sites of chronic inflammation being a common component of tumorigenic microenvironments. In this Review, we give an overview of the impact of sphingolipid metabolism in cancers, from initiation to metastatic dissemination, as well as discussing immune responses and resistance to treatments. We explore how sphingolipids can either help or hinder the progression of cells from a healthy phenotype to a cancerous one.     

Ruled out of preeclampsia‐like syndrome due to COVID‐19: A case study

Coronavirus disease (COVID‐19) is an infectious disease. In this study, we report a 28‐year‐old pregnant woman who had a postpartum seizure with a background of HELLP syndrome and a proven COVID‐19 infection. Her child survived, and at 12‐week postpartum, all maternal COVID‐19–related symptoms vanished, and she was cured.     

Cavernosal nerve functionality evaluation after magnetic resonance imaging-guided transurethral ultrasound treatment of the prostate

AIM: To evaluate the feasibility of using therapeutic ultrasound as an alternative treatment option for organ-confined prostate cancer.METHODS: In this study, a trans-urethral therapeutic ultrasound applicator in combination with 3T magnetic resonance imaging (MRI) guidance was used for real-time multi-planar MRI-based temperature monitoring and temperature feedback control of prostatic tissue thermal ablation in vivo. We evaluated the feasibility and safety of MRI-guided trans-urethral ultrasound to effectively and accurately ablate prostate tissue while minimizing the damage to surrounding tissues in eight canine prostates. MRI was used to plan sonications, monitor temperature changes during therapy, and to evaluate treatment outcome. Real-time temperature and thermal dose maps were calculated using the proton resonance frequency shift technique and were displayed as two-dimensional color-coded overlays on top of the anatomical images. After ultrasound treatment, an evaluation of the integrity of cavernosal nerves was performed during prostatectomy with a nerve stimulator that measured tumescence response quantitatively and indicated intact cavernous nerve functionality. Planned sonication volumes were visually correlated to MRI ablation volumes and corresponding histo-pathological sections after prostatectomy.RESULTS: A total of 16 sonications were performed in 8 canines. MR images acquired before ultrasound treatment were used to localize the prostate and to prescribe sonication targets in all canines. Temperature elevations corresponded within 1 degree of the targeted sonication angle, as well as with the width and length of the active transducer elements. The ultrasound treatment procedures were automatically interrupted when the temperature in the target zone reached 56 °C. In all canines erectile responses were evaluated with a cavernous nerve stimulator post-treatment and showed a tumescence response after stimulation with an electric current. These results indicated intact cavernous nerve functionality. In all specimens, regions of thermal ablation were limited to areas within the prostate capsule and no damage was observed in periprostatic tissues. Additionally, a visual analysis of the ablation zones on contrast-enhanced MR images acquired post ultrasound treatment correlated excellent with the ablation zones on thermal dose maps. All of the ablation zones received a consensus score of 3 (excellent) for the location and size of the correlation between the histologic ablation zone and MRI based ablation zone. During the prostatectomy and histologic examination, no damage was noted in the bladder or rectum.CONCLUSION: Trans-urethral ultrasound treatment of the prostate with MRI guidance has potential to safely, reliably, and accurately ablate prostatic regions, while minimizing the morbidities associated with conventional whole-gland resection or therapy.     

NCI Image-Guided Drug Delivery Summit

On April 17, 2010, scientists from academia, the National Cancer Institute (NCI), and the Food and Drug Administration (FDA) assembled at "The NCI Image Guided Drug Delivery Summit," in Washington D.C., to discuss recent advances, barriers, opportunities, and regulatory issues related to the field. The meeting included a scientific session and an NCI/FDA session, followed by a panel discussion of speakers from both sessions. Image-guided drug delivery (IGDD) in cancer is a form of individualized therapy where imaging methods are used in guidance and monitoring of localized and targeted delivery of therapeutics to the tumor. So, a systematic approach to IGDD requires mechanisms for targeting, delivery, activation, and monitoring of the process. Although the goal in IGDD is to optimize the therapeutic ratio through personalized image-guided treatments, a major challenge is in overcoming the biological barriers to the delivery of therapeutics into tumors and cells. Speakers discussed potential challenges to clinical translation of nano-based drug delivery systems including in vivo characterization of nanocarriers, preclinical validation of targeting and delivery, studies of biodistribution, pharmacokinetics, pharmacodynamics, and toxicity as well as scale-up manufacturing of delivery systems. Physiologic and quantitative imaging techniques may serve as enabling tools that could potentially transform many existing challenges into opportunities for advancement of the field.     

Detection of hepatitis B virus variants in HBV monoinfected and HBV/HIV coinfected Iranian patients under lamivudine treatment

Chronic hepatitis B affects nearly 10% of HIV-infected patients. Hepatitis B virus (HBV) infection is a dynamic disease and coinfection with HIV impacts directly on the outcome of HBV infection, considerably complicating its natural history, diagnosis, and management. The aim of this study was to compare two cohorts of HBV monoinfected and HBV/HIV coinfected Iranian patients undergoing long-term lamivudine therapy from the clinical and virological aspects, as well as the frequency of detected mutations in HBV genome. To this end, HBV Pol/S regions from 72 patients were PCR-amplified and directly sequenced. Phylogenetic analysis indicated a 40-times higher risk of coinfection with ayw3 subtype of HBV genotype D rather than ayw2 subtype [P<0.001, odd: 40.66, CI: 95 % (4.69-352.23)]. While no resistance mutation was detected in HBV/HIV coinfected cohort, LAM-resistance mutations (rtM204I/V in YMDD and rtL180M in FLLA polymerase motifs) were identified in 30% (9 out of 30) and 16.66% (5 out of 30) of HBV monoinfected patients (P<0.05). Moreover, several mutations (sP105A, sI110S/L, sS136Y and sP127T/L) with significant differences in the frequency were identified in the S region of both cohorts. Finally, this study found strong correlation between the type of infection (mono or coinfection) and characteristics like patient gender, ALT levels, HBV-DNA levels and HBV subtypes. These results pointed to the importance of determination of HBV variants in the management of patients and suggested that in contrary to HBV monoinfections, LAM may be still an appropriate drug for the treatment of HBV in HBV/HIV coinfected patients; however, further studies to clarify the role of HIV in HBV LAM-resistance mutations are required.     

Factors related to post-treatment chronic pain in breast cancer survivors: the interference of pain with life functions

The frequency and the intensity of chronic pain, as well as the related factors, were assessed in a cohort of breast cancer patients. The life functions were also questioned in patients who have post-treatment chronic pain. The scope of this retrospective study was a cohort of surgically-treated breast cancer patients with unilateral early stage disease who were under regular follow-up. Patients were eligible if they completed their treatments at least 6 months before and were free of disease. Patients who had a previous history of chronic pain syndrome, chronic debilitating disease, psychiatric diagnosis, and other cancers were excluded. All data regarding their demographics and treatments were recorded. Chronic pain was defined as the pain at treatment-related regions for a duration of at least three months after completion of treatment. Turkish version of "Brief Pain Inventory (Short Form)" was given to the patients with chronic pain in order to assess their pain intensity and life functions. The factors related to chronic pain were compared between patients with and without chronic pain. Eighty-five eligible female patients were included in the study. Thirty-nine (46%) patients declared that they had chronic pain. The mean VAS scale score was 4.1 +/- 2.4 cm in these patients. The mean age of patients with chronic pain (54.3 +/- 12.6 years) was significantly less than that of the ones without pain (60.4 +/- 13.6 years; p = 0.035). Radiotherapy was found to be significantly related to chronic pain (p=0.049; OR: 2.60; 95% CI 1.07-6.30). The VAS scores were 1.5 +/- 2.7 cm, 1.9 +/- 3.2 cm, 1.3 +/- 2.7 cm, 0.9 +/- 2.5 cm for general activity, mood, relations with other people, and sleep, respectively. Although almost half of the early stage breast cancer patients experienced post-treatment chronic pain, they rated the intensity of their pain as mild to moderate. Younger age and receiving radiotherapy were found to be significant contributing factors. The interference of post-treatment chronic pain with life functions was small. Overall, mood was found to be the most affected life function among all.