Cancer by Sfakianakis Alexandros: 03/23/18

Παρασκευή 23 Μαρτίου 2018

Primary male factor infertility due to asthenospermia in maturity-onset diabetes of the young type 5 (MODY 5): uncommon presentation of an uncommon disease

Mutations in hepatocyte nuclear factor-1β gene result in a multisystemic syndrome where a monogenic form of diabetes (maturity-onset diabetes of young type 5; MODY 5) and renal anomalies, usually bilateral multiple cysts are the most characteristic findings. Many of them have pancreatic structural abnormalities as well. A plethora of extrapancreatic manifestations like altered liver function tests, hypomagnesaemia, hyperuricaemia with/without gout and urogenital malformations, particularly in females are also components of the syndrome. Structural malformation of male urogenital tract is rare in MODY 5, even rarer is asthenospermia. We encountered a young non-obese individual having insulin-requiring diabetes following secondary oral agent failure with primary male factor infertility secondary to asthenospermia. A suggestive family history, lack of acanthosis, negative pancreatic autoimmunity, hypomagnesaemia, bilateral renal and epididymal cysts, and absence of body and tail of pancreas pointed towards underlying MODY 5.

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Superficial temporal artery pseudoaneurysm following facial trauma

A 68-year-old man presented with rapid swelling of the right forehead 11 days after sustaining a laceration secondary to a fall. Presumed to be an abscess due to retained foreign body, needle aspiration was performed and arterial blood obtained. Doppler ultrasound revealed a 3 cm mixed echogenicity lesion with 'see-sawing' internal Doppler flow arising from the superficial temporal artery (STA), in keeping with a pseudoaneurysm. Treatment options including interventional radiology and open surgery were considered. Open operative intervention with direct surgical ligation provided an excellent outcome. Delayed pseudoaneurysm of the STA is a rare complication of trauma but should be considered in the differential of a traumatic lateral forehead swelling to prevent complications and inappropriate investigations and management.

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Septic presentation of a giant fibroepithelial polyp of the vulva

Fibroepithelial stromal polyps are mesenchymal lesions occurring typically in reproductive age women with a predilection for the vulvo-vaginal region. Malignancy may mimic this polyp in morphology, rendering further investigations including detailed histopathology mandatory. Histologically its characteristic features are stellate and multinucleate stromal cells identified near the epithelial–stromal interface. This case report discusses incidental finding of largest fibroepithelial polyp presented in a 31-year-old nulliparous woman. She was initially admitted with sepsis and detailed physical examination revealed a right-sided infected pedunculated labial mass measuring 20x21 cm. After initial resuscitation for sepsis, she was further investigated for the mass. Transabdominal ultrasound was essentially normal apart from a small fibroid 3x2 cm in the anterior wall of the uterus. The vulval mass was removed under local and regional anaesthesia and was confirmed to be a giant fibroepithelial stromal polyp on histopathology. The woman recovered well and was followed up until 1 year.

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Thyrotoxic crisis as an acute clinical presentation in a child

A previously well, 4-year-old girl presented with a 4–6 weeks' history of increased appetite, weight loss, tiredness, sleep difficulty, excessive sweating, swelling in the neck and new-onset 'prominent, protruding eyes.' Family history revealed paternal grandmother receiving treatment for hyperthyroidism. Clinical assessment demonstrated features of thyrotoxicosis (tachycardia, warm peripheries, small smooth goitre with no nodules, exophthalmos). TFT (Free T4=101 pmol/L, thyroid-stimulating hormone <0.05 mIU/L) with raised thyroid peroxidase antibody levels (TPO=541 IU/mL) confirmed autoimmune hyperthyroidism. Observation on the ward showed features of thyrotoxic crisis with persistent severe tachycardia on ECG (sinus tachycardia with left ventricular hypertrophy (LVH)) and hypertension. Ultrasound thyroid showed diffuse thyroiditis with no focal lesion. Echocardiogram confirmed the above findings. A diagnosis of Graves' disease with thyrotoxic crisis was made. Antithyroid treatment (carbimazole) and beta-blocker (propranolol) was commenced. Thyrotoxic crisis resolved over 2 weeks and the child has continued to respond to carbimazole treatment at 1-year follow-up.

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Worm in anterior chamber of the eye

We report a case of a 42-year-old female patient who presented to the ophthalmology outpatient department with painful red eye for 1 month. Slit-lamp microscopy showed a live worm in the anterior chamber of left eye. The worm was surgically removed under topical anaesthesia. It was sent to the microbiology department for further identification and was found to be adult female Loaloa.

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Placenta accreta complicated with peripartum cardiomyopathy

A 33-year-old G2P1 was referred to our hospital due to placenta accreta. During perioperative preparations, the patient was diagnosed with having a peripartum cardiomyopathy. The patient underwent caesarean hysterectomy at 36 weeks with an associated 2 L blood loss. Haemodynamic maintenance and stabilisation during the operation were challenging, with the combinations of fluid therapy, blood transfusions as well as vasoactive, antifibrinolytic and haemostatic drug. Postoperatively, the patient was managed in the intensive care unit and was subsequently transferred to intermediate care after less than 24 hours' observation. She was stable enough to be moved to the obstetrics ward the next day.

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Concurrent Sweets syndrome and myopericarditis following mesalamine therapy

Mesalamine, or 5-aminosalicylic acid, is a frequently used medication for the treatment of inflammatory bowel disease (IBD). We report the case of a 40-year-old woman recently diagnosed with IBD and started on mesalamine, who presented with new onset tender skin lesions 3 days following medication administration. One day following the onset of skin lesions, the patient developed acute chest pain, shortness of breath, ECG changes, troponemia, C-reactive protein elevation and pericardial enhancement on cardiac MRI consistent with myopericarditis. Subsequent skin biopsy confirmed the diagnosis of Sweet's syndrome. On cessation of the drug, both the skin lesions and the cardiac symptoms resolved in combination with anti-inflammatory therapy. While mesalamine has been previously associated with myocarditis and pericarditis, to our knowledge this is the first case of coexisting Sweet's syndrome with myopericarditis in the context of mesalamine therapy.

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Rapidly expanding venous intracerebral haemorrhage with spot sign

A 79-year-old woman was brought to the hospital with an acute-onset left haemiparesis. On initial examination, she had a pure sensorimotor syndrome with left-sided weakness and sensory disturbance. Her mental status was normal. She had normal visual fields to confrontation and no neglect. Her initial CT and CT angiogram revealed cerebral venous thrombosis with associated haemorrhage. A 'spot sign' was visible on CT angiogram. Immediately following the CT scan, the patient had a rapidly progressive decline in level of consciousness, requiring endotracheal intubation. A follow-up CT scan 70 min later showed the haemorrhage had expanded dramatically, with mass effect, midline shift and herniation. After a discussion with the family, the patient was extubated and died the following day. This is the first case of a cerebral venous thrombosis with associated spot sign-positive haemorrhage and published clinical details that the authors are aware of.

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Autoimmune pancreatitis with concomitant autoimmune haemolytic anaemia

Autoimmune pancreatitis (AIP) is an infrequent cause of acute pancreatitis, being more commonly associated with chronic pancreatitis. AIP can be associated with other autoimmune manifestations, including Sjögren's, inflammatory bowel disease, primary biliary cirrhosis, rheumatoid arthritis, hypothyroidism and sarcoidosis. Rarely, concurrent autoimmune haemolytic anaemia (AIHA) is observed, as seen in our case report of a 33-year-old postpartum woman.

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Pneumatosis intestinalis in small bowel obstruction

Description

We present a case of a 42-year-old woman with a history of acute myeloid leukaemia treated with bone marrow transplant. Her case was complicated by graft versus host disease involving the gastrointestinal tract, necessitating partial colectomy with ileostomy. She presented to the hospital with recurrent partial small bowel obstruction (SBO). Abdominal CT scan was consistent with partial SBO, and the patient was admitted for conservative treatment. She was deemed a poor surgical candidate given her multiple comorbidities and immunosuppressed state. Her clinical condition waxed and waned over the next week, and on hospital day 10 the patient developed decreased ileostomy output, increased nausea and vomiting. Abdominal radiographs revealed dilated bowel with increased intramural radiolucency (figure 1), and subsequent CT scan was confirmatory for extensive pneumatosis intestinalis (PI) (figure 2). The patient was treated conservatively with bowel rest and nasogastric suction with favourable outcome.

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Delayed neurological deficits after endovascular placement of a pipeline embolisation device: clinical manifestation and treatment

Endovascular treatment has been the mainstay of therapy for repair of both ruptured and unruptured cerebral aneurysms. Flow diverter devices offer a new option for the treatment of complex aneurysms that were previously not amenable to coiling. Procedural adverse effects include intracranial haemorrhage and ischaemic stroke, which usually occur on the same day. Delayed complications are rare. We report a case of a patient who underwent placement of a pipeline embolisation device and developed delayed neurological deficits, which were thought to be an inflammatory reaction to the hydrophilic coating used in guidewires and microcatheters. Our patient was treated with a course of steroids, with improvement of her neurological deficits and resolution of MRI findings. As the use of flow diverter devices has increased, variable and delayed complications of such therapy are increasingly being reported in the literature.

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Frailty and Comorbidities Among Survivors of Adolescent and Young Adult Cancer: A Cross-Sectional Examination of a Hospital-Based Survivorship Cohort

Journal of Adolescent and Young Adult Oncology, Ahead of Print.

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Survivorship Care Planning for Young Adults After Cancer Treatment: Understanding Care Patterns and Patient-Reported Outcomes

Journal of Adolescent and Young Adult Oncology, Ahead of Print.

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Frailty and Comorbidities Among Survivors of Adolescent and Young Adult Cancer: A Cross-Sectional Examination of a Hospital-Based Survivorship Cohort

Journal of Adolescent and Young Adult Oncology, Ahead of Print.

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Survivorship Care Planning for Young Adults After Cancer Treatment: Understanding Care Patterns and Patient-Reported Outcomes

Journal of Adolescent and Young Adult Oncology, Ahead of Print.

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Pathological assessment of gastrointestinal biopsies from patients with idelalisib-associated diarrhea and colitis

Future Oncology, Ahead of Print.

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S100A11 promotes TGF-β1-induced epithelial-mesenchymal transition through SMAD2/3 signaling pathway in intrahepatic cholangiocarcinoma

Future Oncology, Ahead of Print.

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Regorafenib in the treatment of metastatic colorectal cancer

Future Oncology, Ahead of Print.

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Pathological assessment of gastrointestinal biopsies from patients with idelalisib-associated diarrhea and colitis

Future Oncology, Ahead of Print.

https://ift.tt/2FZgMNu

S100A11 promotes TGF-β1-induced epithelial-mesenchymal transition through SMAD2/3 signaling pathway in intrahepatic cholangiocarcinoma

Future Oncology, Ahead of Print.

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A case of mature cystic teratoma with intestinal structures harboring intestinal-type low-grade mucinous neoplasm

Abstract

The formation of gastrointestinal-type epithelium is found in 7–13% of mature cystic teratomas, which are the most common germ cell tumors of the ovary. Few cases harboring organized gastrointestinal tract formation have been reported, and a mucinous neoplasm arising in them is further rare. Here, we report a case of an ovarian mature cystic teratoma with intestinal structures harboring intestinal-type mucinous neoplasm, mimicking low-grade appendiceal mucinous cystadenoma. A 66-year-old female, with remarkably increased serum carcinoembryonic antigen (CEA) level, underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy due to the ovarian tumor. The immunoprofile of the tumor showed CK7−/CK20+. We review the past literatures, and then consider that the existence of mucinous neoplasm should be kept in mind if we find elevated level of serum CEA and the organized gastrointestinal development in an ovary. The immunoprofile of CK7/CK20 is useful to determine the origin of mucinous tumors associated with mature cystic teratomas.

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Regorafenib in the treatment of metastatic colorectal cancer

Future Oncology, Ahead of Print.

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Pathological assessment of gastrointestinal biopsies from patients with idelalisib-associated diarrhea and colitis

Future Oncology, Ahead of Print.

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S100A11 promotes TGF-β1-induced epithelial-mesenchymal transition through SMAD2/3 signaling pathway in intrahepatic cholangiocarcinoma

Future Oncology, Ahead of Print.

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Diacylglycerol kinase α inactivation is an integral component of the costimulatory pathway that amplifies TCR signals

Abstract

The arsenal of cancer therapies has evolved to target T lymphocytes and restore their capacity to destroy tumor cells. T cells rely on diacylglycerol (DAG) to carry out their functions. DAG availability and signaling are regulated by the enzymes diacylglycerol kinase (DGK) α and ζ, whose excess function drives T cells into hyporesponsive states. Targeting DGKα is a promising strategy for coping with cancer; its blockade could reinstate T-cell attack on tumors while limiting tumor growth, due to positive DGKα functions in several oncogenic pathways. Here, we made a side-by-side comparison of the effects of commercial pharmacological DGK inhibitors on T-cell responses with those promoted by DGKα and DGKζ genetic deletion or silencing. We show the specificity for DGKα of DGK inhibitors I and II and the structurally similar compound ritanserin. Inhibitor treatment promoted Ras/ERK (extracellular signal-regulated kinase) signaling and AP-1 (Activator protein-1) transcription, facilitated DGKα membrane localization, reduced the requirement for costimulation, and cooperated with enhanced activation following DGKζ silencing/deletion. DGKiII and ritanserin had similar effects on TCR proximal signaling, but ritanserin counteracted long-term T-cell activation, an effect that was potentiated in DGKα^−/− cells. In contrast with enhanced activation triggered by pharmacological inhibition, DGKα silencing/genetic deletion led to impaired Lck (lymphocyte-specific protein tyrosine kinase) activation and limited costimulation responses. Our results demonstrate that pharmacological inhibition of DGKα downstream of the TCR provides a gain-of-function effect that amplifies the DAG-dependent signaling cascade, an ability that could be exploited therapeutically to reinvigorate T cells to attack tumors.

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Durvalumab May Be Effective in Patients with EGFR+/ALK+ NSCLC [Research Watch]

PD-L1 blockade with durvalumab achieves responses in patients with EGFR⁺/ALK⁺ and EGFR^–/ALK^– NSCLC.

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PTEN deficiency and AMPK activation promote nutrient scavenging and anabolism in prostate cancer cells [Research Articles]

We report that PTEN-deficient prostate cancer cells use macropinocytosis to survive and proliferate under nutrient stress. PTEN loss increased macropinocytosis only in the context of AMPK activation revealing a general requirement for AMPK in macropinocytosis and a novel mechanism by which AMPK promotes survival under stress. In prostate cancer cells, albumin uptake did not require macropinocytosis, but necrotic cell debris proved a specific macropinocytic cargo. Isotopic labeling confirmed that macropinocytosed necrotic cell proteins fueled new protein synthesis in prostate cancer cells. Supplementation with necrotic debris, but not albumin, also maintained lipid stores suggesting that macropinocytosis can supply nutrients other than amino acids. Non-transformed prostatic epithelial cells were not macropinocytic, but patient-derived prostate cancer organoids and xenografts and autochthonous prostate tumors all exhibited constitutive macropinocytosis, and blocking macropinocytosis limited prostate tumor growth. Macropinocytosis of extracellular material by prostate cancer cells is a previously unappreciated tumor-microenvironment interaction that could be targeted therapeutically.

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Protein Phosphatase 2A Is Essential for B-cell Tumor Redox Homeostasis [Research Watch]

PP2A mediates a metabolic switch from glycolysis to the PPP in B-cell malignancies.

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ctDNA Analysis for Cancer? Not So Fast [News in Brief]

Expert panel calls for more research before these tests are adopted in clinical practice.

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IL18 Promotes MDSC-Mediated Immunosuppression in Multiple Myeloma [Research Watch]

IL18 drives bone marrow MDSC function to suppress T-cell activity and accelerate multiple myeloma.

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Checkpoint Inhibitors May Induce Myocarditis [News in Brief]

Database is helping researchers investigate rare but serious cardiac side effects associated with the drugs.

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The MDA-9/Syntenin/IGF-1R/STAT3 axis directs prostate cancer invasion

Although prostate cancer (PCa) is clinically manageable during several stages of progression, survival is severely compromised once cells invade and metastasize to distant organs. Comprehending the pathobiology of invasion is required for developing efficacious targeted therapies against metastasis. Based on bioinformatics data, we predicted an association of melanoma differentiation associated gene-9 (syntenin, or syndecan binding protein (SDCBP)) in PCa progression. Using tissue samples from various Gleason stage PCa patients with adjacent normal tissue, a series of normal prostate and PCa cell lines (with differing tumorigenic/metastatic properties), mda-9/syntenin manipulated variants (including loss-of-function and gain-of-function cell lines), and CRISPR/Cas9 stable MDA-9/syntenin knockout cells, we now confirm the relevance of and dependence on MDA-9/syntenin in PCa invasion. MDA-9/syntenin physically interacted with insulin-like growth factor-1 receptor (IGF-1R) following treatment with insulin-like growth factor binding protein-2 (IGFBP-2), regulating downstream signaling processes that enabled STAT3 phosphorylation. This activation enhanced expression of MMP-2 and MMP-9, two established enzymes that positively regulate invasion. Additionally, MDA-9/syntenin-mediated upregulation of pro-angiogenic factors including IGFBP-2, IL-6, IL-8, and VEGF-A also facilitated migration of PCa cells. Collectively, our results draw attention to MDA-9/syntenin as a positive regulator of PCa metastasis, and the potential application of targeting this molecule to inhibit invasion and metastasis in PCa and potentially other cancers.

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Human Elongation Factor 4 Regulates Cancer Bioenergetics by Acting as a Mitochondrial Translation Switch

Mitochondria regulate cellular bioenergetics and redox states and influence multiple signaling pathways required for tumorigenesis. In this study, we determined that the mitochondrial translation elongation factor 4 (EF4) is a critical component of tumor progression. EF4 was ubiquitous in human tissues with localization to the mitochondria (mtEF4) and performed quality control on respiratory chain biogenesis. Knockout of mtEF4 induced respiratory chain complex defects and apoptosis, while its overexpression stimulated cancer development. In multiple cancers, expression of mtEF4 was increased in patient tumor tissues. These findings reveal that mtEF4 expression may promote tumorigenesis via an imbalance in the regulation of mitochondrial activities and subsequent variation of cellular redox. Thus, dysregulated mitochondrial translation may play a vital role in the etiology and development of diverse human cancers.

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A large-scale, exome-wide association study of Han Chinese women identifies three novel loci predisposing to breast cancer

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g. ESR1, FGFR2 and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10-8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10-9) and one new non-coding variant at 7q21.11 (P < 5 × 10-8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 x 10-8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 x 10-8) and CNFN (P = 3.77 x 10-4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.

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IL-22RA1/ STAT3 signaling promotes stemness and tumorigenicity in pancreatic cancer

Chronic inflammation is a feature of pancreatic cancer, but little is known about how immune cell or immune cell-related signal affects pancreatic cancer stemness and development. Our previous work showed that IL-22/IL-22RA1 plays a vital role in acute and chronic pancreatitis progression by mediating crosstalk between immune cells and acinar cells or stellate cells, respectively. Here we find IL-22RA1 is highly but heterogeneously expressed in pancreatic cancer cells, with high expression associated with poor prognosis of pancreatic cancer patients. The IL-22RA1hi population from pancreatic tumor harbored higher stemness potential and tumorigenicity. Notably, IL-22 promoted pancreatic cancer stemness via IL-22RA1/STAT3, which identified a functional signaling to regulate cancer stemness by microenvironmental factor. Moreover, STAT3 was indispensable for the maintenance of IL-22RA1hi cells. Overall, these findings provide a therapeutic strategy for PDAC patients with high expression of IL-22RA1.

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Therapeutic targeting of sunitinib-induced AR phosphorylation in renal cell carcinoma

Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer. AR expression has also been reported in other solid tumors, including renal cell carcinoma (RCC), but its biological role here remains unclear. Through integrative analysis of a reverse phase protein array (RPPA), we discovered increased expression of AR in an RCC patient-derived xenograft model of acquired resistance to the receptor tyrosine kinase inhibitor (RTKi) sunitinib. AR expression was increased in RCC cell lines with either acquired or intrinsic sunitinib resistance in vitro. An AR signaling gene array profiler indicated elevated levels of AR target genes in sunitinib-resistant cells. Sunitinib-induced AR transcriptional activity was associated with increased phosphorylation of serine 81 (pS81) on AR. Additionally, AR overexpression resulted in acquired sunitinib resistance, and the AR antagonist enzalutamide-induced AR degradation and attenuated AR downstream activity in sunitinib-resistant cells, also indicated by decreased secretion of human kallikrein 2 (KLK2). Enzalutamide-induced AR degradation was rescued by either proteasome inhibition or by knockdown of the AR ubiquitin ligase speckle-type POZ protein (SPOP). In vivo treatment with enzalutamide and sunitinib demonstrated that this combination efficiently induced tumor regression in an RCC model following acquired sunitinib resistance. Overall, our results suggest the potential role of AR as a target for therapeutic interventions, in combination with RTKi, to overcome drug resistance in RCC.

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Transition of mesenchymal and epithelial cancer cells depends on {alpha}1-4 galactosyltransferase-mediated glycosphingolipids

The reversible transitions of cancer cells between epithelial and mesenchymal states comprise cellular and molecular processes essential for local tumor growth and respective dissemination. We report here that globoside glycosphingolipid (GSL) glycosyltransferase-encoding genes are elevated in epithelial cells and correlate with characteristic EMT signatures predictive of disease outcome. Depletion of globosides through CRISPR-Cas9-mediated deletion of the key enzyme A4GALT induces EMT, enhances chemoresistance, and increased CD24low/CD44high cells. The cholera toxin-induced mesenchymal-to-epithelial transition occurred only in cells with functional A4GALT. Cells undergoing EMT lost E-cadherin expression through epigenetic silencing at the promoter region of CDH1. However, in ΔA4GALT cells, demethylation was able to rescue E-cadherin-mediated cell-cell adhesion only in the presence of exogenous A4GALT. Overall, our data suggest another class of biomolecules vital for epithelial cancer cells and for maintaining cell integrity and function.

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The MDA-9/Syntenin/IGF-1R/STAT3 axis directs prostate cancer invasion

Human Elongation Factor 4 Regulates Cancer Bioenergetics by Acting as a Mitochondrial Translation Switch

A large-scale, exome-wide association study of Han Chinese women identifies three novel loci predisposing to breast cancer

IL-22RA1/ STAT3 signaling promotes stemness and tumorigenicity in pancreatic cancer

Therapeutic targeting of sunitinib-induced AR phosphorylation in renal cell carcinoma

Survivorship care plans: are randomized controlled trials assessing outcomes that are relevant to stakeholders?

Abstract

Purpose

The purpose of this study was to compare outcomes assessed in extant randomized controlled trials (RCTs) to outcomes that stakeholders expect from survivorship care plans (SCPs). To facilitate the transition from active treatment to follow-up care for the 15.5 million US cancer survivors, many organizations require SCP use. However, results of several RCTs of SCPs' effectiveness have been null, possibly because they have evaluated outcomes on which SCPs should be expected to have limited influence. Stakeholders (e.g., survivors, oncologists) may expect outcomes that differ from RCTs' outcomes.

Methods

We identified RCTs' outcomes using a PubMed literature review. We identified outcomes that stakeholders expect from SCPs using semistructured interviews with stakeholders in three healthcare systems in the USA and Canada. Finally, we mapped RCTs' outcomes onto stakeholder-identified outcomes.

Results

RCT outcomes did not fully address outcomes that stakeholders expected from SCPs, and RCTs assessed outcomes that stakeholders did not expect from SCPs. RCTs often assessed outcomes only from survivors' perspectives.

Conclusions

RCTs of SCPs' effectiveness have not assessed outcomes that stakeholders expect. To better understand SCPs' effectiveness, future RCTs should assess outcomes of SCP use that are relevant from the perspective of multiple stakeholders.

Implications for Cancer Survivors

SCPs' effectiveness may be optimized when used with an eye toward outcomes that stakeholders expect from SCPs. For survivors, this means using SCPs as a map to guide them with respect to what kind of follow-up care they should seek, when they should seek it, and from whom they should seek it.

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Survivorship care plans: are randomized controlled trials assessing outcomes that are relevant to stakeholders?

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https://ift.tt/2pFfFI6

Correction to: From IB2 to IIIB locally advanced cervical cancers: report of a ten-year experience

Abstract

In the original publication [1] one author name was spelled incorrect.

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Radioiodine Refractory Differentiated Thyroid Cancer

Publication date: Available online 22 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Yuchen Jin, Douglas Van Nostrand, Lingxiao Cheng, Min Liu, Libo Chen
Differentiated thyroid cancer (DTC) is usually curable with surgery, radioactive iodine (RAI), and thyroid-stimulating hormone (TSH) suppression. However, local recurrence and/or distant metastases occur in approximately 15% of cases during follow-up, and nearly two-thirds of these patients will become RAI-refractory (RR-DTC) with a poor prognosis. This review focuses on the most challenging and rapidly evolving aspects of RR-DTC, and we discuss the considerable improvement in more accurately defining RR-DTC, more effective therapeutic strategies, and describe the diagnosis, pathogenesis, and future prospects of RR-DTC. Along with the detection of serum thyroglobulin and anatomic imaging modalities, such as ultrasound and computer tomography, radionuclide molecular imaging plays a vital role in the evaluation of RR-DTC. In addition, continual progress has been made in the management of RR-DTC, including watchful waiting under appropriate TSH suppression, local treatment approaches, and systemic therapies (molecular targeted therapy, redifferentiation therapy, gene therapy, and cancer immunotherapy). These all hold promise to change the natural history of RR-DTC.

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When and how to treat women with HER2-positive, small (pT1a-b), node-negative breast cancer?

Publication date: Available online 22 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Stefania Gori, Monica Turazza, Alessandra Modena, Simona Duranti, Giuseppe Zamboni, Filippo Alongi, Giovanni Carbognin, Alberto Massocco, Matteo Salgarello, Alessandro Inno
Small (pT1a-b), node-negative (pN0) breast cancer generally has a good prognosis. However, HER2-positive status is associated with an increased risk of relapse and decreased survival even in these tumors. Although there are only few data from prospective randomized trials, results of retrospective studies suggest adjuvant chemotherapy plus trastuzumab may improve outcomes of patients with pT1a-b pN0 HER2-positive breast cancer. On the other hand, trastuzumab is potentially associated with increased cardiac toxicity, especially when combined with anthracycline-based chemotherapy. A valid strategy for improving cardiac safety is the addition of trastuzumab to non-anthracycline chemotherapy, whereas a shorter duration of trastuzumab should be not routinely considered although might represent an option for selected patients at low risk of relapse and very high risk of cardiac events. Therefore, the choice of adjuvant treatment for patients with pT1a-b pN0 HER2-positive breast cancer should be done on individual basis, carefully weighing benefits and risks.

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Biological aspects of chondrosarcoma: leaps and hurdles

Publication date: Available online 22 March 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Benoîte Mery, Sophie Espenel, Jean-Baptiste Guy, Chloé Rancoule, Alexis Vallard, Marie-Thérèse Aloy, Claire Rodriguez-Lafrasse, Nicolas Magné
Chondrosarcomas are characterized by their chemo- and radioresistance leading to a therapeutic surgical approach which remains the only available treatment with a 10-year survival between 30% and 80% depending on the grade. Non-surgical treatments are under investigation and rely on an accurate biological understanding of drug resistance mechanisms. Novel targeted therapy which represents a new relevant therapeutic approach will open new treatment options by targeting several pathways responsible for processes of proliferation and invasion. Survival pathways such as PI3K, AKT, mTOR and VEGF have been shown to be involved in proliferation of chondrosarcoma cells and antiapoptotic proteins may also play a relevant role. Other proteins such as p53 or COX2 have been identified as potential new targets. This review provides an insight into the biological substantial treatment challenges of CHS and focuses on improving our understanding of CH biology through an overview of major signaling pathways that could represent targets for new therapeutic approaches.

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Παρασκευή 23 Μαρτίου 2018

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