Role of right hemicolectomy in patients with low-grade appendiceal mucinous adenocarcinoma

Background: Dysregulated lipid metabolism is emerging as a hallmark in several malignancies, including ovarian cancer (OC). Specifically, metastatic OC is highly dependent on lipid-rich omentum. We aimed to investigate the therapeutic value of targeting lipid metabolism in OC. For this purpose, we studied the role of PCSK9, a cholesterol-regulating enzyme, in OC cell survival and its downstream signaling. We also investigated the cytotoxic efficacy of a small library of metabolic (n = 11) and mTOR (n = 10) inhibitors using OC cell lines (n = 8) and ex vivo patient-derived cell cultures (PDCs, n = 5) to identify clinically suitable drug vulnerabilities. Targeting PCSK9 expression with siRNA or PCSK9 specific inhibitor (PF-06446846) impaired OC cell survival. In addition, overexpression of PCSK9 induced robust AKT phosphorylation along with increased expression of ERK1/2 and MEK1/2, suggesting a pro-survival role of PCSK9 in OC cells. Moreover, our drug testing revealed marked differences in cytotoxic responses to drugs targeting metabolic pathways of high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC) PDCs. Our results show that targeting PCSK9 expression could impair OC cell survival, which warrants further investigation to address the dependency of this cancer on lipogenesis and omental metastasis. Moreover, the differences in metabolic gene expression and drug responses of OC PDCs indicate the existence of a metabolic heterogeneity within OC subtypes, which should be further explored for therapeutic improvements.

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Impact of sex in the prevalence and progression of glioblastomas: the role of gonadal steroid hormones

Biology of Sex Differences ◽

10.1186/s13293-021-00372-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Claudia Bello-Alvarez ◽

Ignacio Camacho-Arroyo

Keyword(s):

Cell Proliferation ◽

Steroid Hormones ◽

Physiological State ◽

Migration And Invasion ◽

Low Grade ◽

Main Body ◽

Protective Effects ◽

Gonadal Steroid Hormones ◽

Gonadal Steroid

Abstract Background As in other types of cancers, sex is an essential factor in the origin and progression of glioblastomas. Research in the field of endocrinology and cancer suggests that gonadal steroid hormones play an important role in the progression and prevalence of glioblastomas. In the present review, we aim to discuss the actions and mechanism triggered by gonadal steroid hormones in glioblastomas. Main body Glioblastoma is the most common malignant primary brain tumor. According to the epidemiological data, glioblastomas are more frequent in men than in women in a 1.6/1 proportion both in children and adults. This evidence, and the knowledge about sex influence over the prevalence of countless diseases, suggest that male gonadal steroid hormones, such as testosterone, promote glioblastomas growth. In contrast, a protective role of female gonadal steroid hormones (estradiol and progesterone) against glioblastomas has been questioned. Several pieces of evidence demonstrate a variety of effects induced by female and male gonadal steroid hormones in glioblastomas. Several studies indicate that pregnancy, a physiological state with the highest progesterone and estradiol levels, accelerates the progression of low-grade astrocytomas to glioblastomas and increases the symptoms associated with these tumors. In vitro studies have demonstrated that progesterone has a dual role in glioblastoma cells: physiological concentrations promote cell proliferation, migration, and invasion while very high doses (out physiological range) reduce cell proliferation and increases cell death. Conclusion Gonadal steroid hormones can stimulate the progression of glioblastomas through the increase in proliferation, migration, and invasion. However, the effects mentioned above depend on the concentrations of these hormones and the receptor involved in hormone actions. Estradiol and progesterone can exert promoter or protective effects while the role of testosterone has been always associated to glioblastomas progression.

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Inflammatory Mediators and Insulin Resistance in Obesity: Role of Nuclear Receptor Signaling in Macrophages

Mediators of Inflammation ◽

10.1155/2010/219583 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 51

Author(s):

Lucía Fuentes ◽

Tamás Rőszer ◽

Mercedes Ricote

Keyword(s):

Insulin Resistance ◽

Nuclear Receptor ◽

Cytokine Production ◽

Current Knowledge ◽

Liver Steatosis ◽

Visceral Obesity ◽

M2 Macrophage ◽

Low Grade ◽

The Impact

Visceral obesity is coupled to a general low-grade chronic inflammatory state characterized by macrophage activation and inflammatory cytokine production, leading to insulin resistance (IR). The balance between proinflammatory M1 and antiinflammatory M2 macrophage phenotypes within visceral adipose tissue appears to be crucially involved in the development of obesity-associated IR and consequent metabolic abnormalities. The ligand-dependent transcription factors peroxisome proliferator activated receptors (PPARs) have recently been implicated in the determination of the M1/M2 phenotype. Liver X receptors (LXRs), which form another subgroup of the nuclear receptor superfamily, are also important regulators of proinflammatory cytokine production in macrophages. Disregulation of macrophage-mediated inflammation by PPARs and LXRs therefore underlies the development of IR. This review summarizes the role of PPAR and LXR signaling in macrophages and current knowledge about the impact of these actions in the manifestation of IR and obesity comorbidities such as liver steatosis and diabetic osteopenia.

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Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0032 ◽

2013 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

Charmaine S. Tam ◽

Leanne M. Redman

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Low Grade ◽

Metabolic Dysfunction ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Proinflammatory Mediators ◽

Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

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Endokrinológiai tényezők és metabolikus folyamatok szerepe az élettartam szabályozásában

Orvosi Hetilap ◽

10.1556/650.2021.32200 ◽

2021 ◽

Vol 162 (33) ◽

pp. 1318-1327

Author(s):

Tamás Halmos ◽

Ilona Suba

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Life Expectancy ◽

Significant Risk ◽

Low Grade ◽

Aging Effects ◽

Protective Function ◽

Beneficial Effects ◽

Age Related

Összefoglaló. Az emberek a lehető leghosszabb ideig akarnak élni, jó egészségben. Ha kiküszöbölnénk a kedvezőtlen külső körülményeket, a várható élettartam meghaladhatná a 100 évet. A 20. és 21. században a jóléti társadalmakban a várható élettartam jelentősen megnőtt, így Magyarországon is. Az áttekintett irodalom alapján megvizsgáltuk, hogy a genetika és az öröklődés mellett milyen endokrinológiai és metabolikus tényezők játszanak szerepet az élet meghosszabbításában. Megvizsgáltunk minden endogén tényezőt, amely pozitívan vagy negatívan befolyásolhatja az életkorral összefüggő betegségeket (Alzheimer-kór, szív- és érrendszeri betegségek, rák) és az élettartamot. Kiemeltük a hyperinsulinaemia, az inzulinrezisztencia, a metabolikus szindróma öregedést gyorsító hatását, az inzulinszerű növekedési hormon-1 ellentmondásos szerepét, valamint az élet meghosszabbításában részt vevő, újabban felfedezett peptideket, mint a klotho és a humanin. Ismertettük a mitochondriumok szerepét az élettartam meghatározásában, bemutattuk a mitohormesis folyamatát és annak stresszvédő funkcióját. Bemutattuk a rapamicin célszervét, az mTOR-t, amelynek gátlása meghosszabbítja az élettartamot, valamint a szirtuinokat. Kitértünk az autophagia folyamatára, és ismertettük a szenolitikumok szerepét az öregedésben. Az időskori autoimmunitás csökkenése hozzájárul az élettartam rövidüléséhez, utaltunk a thymus koordináló szerepére. Kiemeltük a bélmikrobiom fontos szerepét az élettartam szabályozásában. Hivatkoztunk a „centenáriusok” megfigyeléséből nyert humánadatokra. Megvizsgáltuk, milyen beavatkozási lehetőségek állnak rendelkezésre az egészségben tölthető élettartam meghosszabbításához. Az életmódbeli lehetőségek közül kiemeltük a kalóriabevitel-csökkentés és a testmozgás jótékony szerepét. Megvizsgáltuk egyes gyógyszerek feltételezett hatásait. Ezek közé tartozik a metformin, az akarbóz, a rezveratrol. E gyógyszerek mindegyikének hatása hasonló a kalóriamegszorításéhoz. Nincs olyan „csodaszer”, amely igazoltan meghosszabbítja az élettartamot emberben. Egyes géneknek és génmutációknak jótékony hatásuk van, de ezt környezeti tényezők, betegségek, balesetek és más külső ártalmak módosíthatják. Kiemeljük az elhízás, az alacsony fokozatú gyulladás és az inzulinrezisztencia öregedésre gyakorolt gyorsító hatását. A metabolikus szindróma elterjedtsége miatt ez jelentős népegészségügyi kockázatot jelent. Az inzulin, a növekedési hormon és az inzulinszerű növekedési faktorok hatásainak értékelése továbbra is ellentmondásos. Az egészséges, szellemileg és fizikailag aktív életmód, a kalóriacsökkentés mindenképpen előnyös. Az életet meghosszabbító szerek értékelése még vitatott. Orv Hetil. 2021; 162(33): 1318–1327. Summary. People want to live as long as possible in good health. If we eliminate the unfavorable external conditions, the life expectancy could exceed 100 years. In the 20th and 21th centuries, life expectancy in welfare societies increased significantly, including in Hungary. Based on the reviewed literature, we examined what endocrinological and metabolic factors play a role in prolonging life in addition to genetics and inheritance. We examined all endogenous factors that can positively or negatively affect age-related diseases (Alzheimer’s disease, cardiovascular disease, cancer) and longevity. We highlighted the aging effects of hyperinsulinemia, insulin resistance, metabolic syndrome, the controversial role of insulin-like growth factor-1, and more recently discovered peptides involved in prolonging lifespan, such as klotho and humanin. We described the role of mitochondria in determining longevity, we demonstrated the process of mitohormesis and its stress-protective function. We presented the target organ of rapamycin, mTOR, the inhibition of which prolongs lifespan, as well as sirtuins. We covered the process of autophagy and described the role of senolytics in aging. The decrease in autoimmunity in old age contributes to the shortening of life expectancy, we referred to the coordinating role of the thymus. We highlighted the important role of intestinal microbiome in the regulation of longevity. We referred to human data obtained from observations on “centenarians”. We examined what intervention options are available to prolong healthy life expectancy. Among the lifestyle options, we highlighted the beneficial role of calorie reduction and exercise. We examined the putative beneficial effects of some drugs. These include metformin, acarbose, resveratrol. The effect of each of these drugs is similar to calorie restriction. There is no “miracle cure” that has been shown to prolong life-span in humans. Some genes and gene mutations have beneficial effects, but this can be modified by environmental factors, diseases, accidents, and other external harms. We highlight the accelerating effects of obesity, low-grade inflammation, and insulin resistance on aging. Due to the prevalence of metabolic syndrome, this poses a significant risk to public health. The assessment of the effects of insulin, growth hormone, and insulin-like growth factors remains controversial. A healthy, mentally and physically active lifestyle, calorie reduction is definitely beneficial. The evaluation of life-prolonging agents is still controversial. Orv Hetil. 2021; 162(33): 1318–1327.

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Role of susceptibility weighted imaging (SWI) in assessment of intra axial brain neoplasms in adults

QJM ◽

10.1093/qjmed/hcab106.056 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Pasant Mohamed Abo-Elhoda Darwish Mohamed Abo-Elhoda ◽

Hesham Mahmoud Ahmed Mansour ◽

Yosra Abdelzaher Abdullah ◽

Eman Ahmed Fouad Darwish

Keyword(s):

Brain Neoplasms ◽

Tumor Size ◽

Venous Blood ◽

Brain Parenchyma ◽

P Value ◽

Susceptibility Weighted Imaging ◽

Low Grade ◽

Chi Square ◽

Cross Sectional

Abstract Background Susceptibility weighted imaging (SWI) is a 3D gradient-echo MR technique that is based on blood oxygen level dependent (BOLD) induced phase effects between the venous blood and the surrounding brain parenchyma. SW-MR imaging allows for noninvasive visualization of small veins at submillimeter resolution and, therefore, is used to depict venous architecture in brain lesions. The extreme sensitivity of SWI for the detection of neovascularity (venous blood), haemorrhage, and calcification has been an indispensable tool for characterization of the internal architecture of brain tumours. Objectives Is to evaluate the role of Susceptibility weighted imaging in assessment of adults Intra axial brain Neoplasms, and its ability to characterize them into high and low grade lesions in comparison to histopathology which will be used as gold standard. Methods A cross sectional study including 31 patients suspecting intracranial brain neoplasm radiologically and clinically, conducted at Private center, the patients were investigated using Siemens machine Magnetom Skyra 3T, the period was between January 2018 till the end of June 2019 . Results Our study included 31 patients. Including 15 female and 16 male patients, with the patient’s age ranging from 20 to 68 years old with median 48 years old ranging from 35.75 (25% percentile) to 58.75 (75% percentile). Among total cases, there were 8 patients with grade 2 glioma, 10 patients with grade 3 glioma and 6 patients with grade 4 glioma, 2 patients with lymphoma and 5 patients with brain metastasis (1 lung cancer and 4 breast cancer). All the patients were evaluated with MRI including SWI sequence with special comment on the number of the intratumoral susceptibility signal (ITSS), the size of the ITSS, its morphology as well as the ratio of the ITSS to the tumor size, which were then correlated with the patient histopathological results obtained later. The study revealed that the best parameter to accurately grade the tumor is the number of ITSS within the lesion with P value 0.001, followed by the size of the ITSS with P value 0.002 and Pearson Chi-Square value equals 20.6, while the lowest one was the ratio of the ITSS to the tumor size with P value 0.002 Pearson Chi-Square value equals 17.3. Our study showed that the morphology alone was not able to accurately grade the tumor with P value 0.007 ( Not significant) Conclusion SWI using 3T MR system provides quite useful information for preoperative tumor grading. There seems to be a strong correlation between pathological grading and that assessed with SWI.

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EP.FRI.999 Case report of a Low Grade appendiceal mucinous neoplasm (LAMN) and review of literature

British Journal of Surgery ◽

10.1093/bjs/znab312.144 ◽

2021 ◽

Vol 108 (Supplement_7) ◽

Author(s):

Kimberly Da Costa ◽

Sivakumaran Sabanathan

Keyword(s):

Intraperitoneal Chemotherapy ◽

Pseudomyxoma Peritonei ◽

Right Hemicolectomy ◽

Low Grade ◽

Mucinous Neoplasm ◽

Mucinous Neoplasms ◽

Mucocele Of The Appendix ◽

Preoperative Ct ◽

Inflammatory Processes ◽

Progressive Accumulation

Abstract A mucocele refers to an appendix that has dilated due to progressive accumulation of mucus within its lumen. Appendiceal mucocele is a rare cause of an acute abdomen. They represent 0.2-0.7% of all appendix specimens. LAMN account for less than 0.3% of appendicectomy specimens. We present a 38 year old man with an acute RIF’s pain who went on to have CT scan which revealed a mucocele of appendix but did not show any features of perforation or pseudomyxoma peritonei. He had a laparoscopic converted to open appendicectomy. The proximal 2 cm of appendix was oedematous but normal calibre. Histology revealed a low grade appendiceal mucinous neoplasm (LAMN) that was completely excised. The mucocele of the appendix was first described by Rokitansky in 1842. Appendix mucocele may come as a consequence of obstructive or inflammatory processes, cystadenomas or cystadenocarcinomas. Appendiceal mucinous neoplasms commonly presents in the sixth decade of life and our patient was much younger in comparison. Several literatures suggest the value of preoperative CT imaging in obtaining diagnosis and also in planning further treatment. Appendicectomy or a right hemicolectomy is treatment of choice based on presence or absence of following factors 1. Perforated mucocele 2. Involvement of the base of the appendix. 3. Positive lymph nodes of mesoappendix and ileocolic. Patients with malignancy or pseudomyxoma peritonei are likely to require cytoreductive surgery, heated intraoperative intraperitoneal chemotherapy, early postoperative intraperitoneal chemotherapy.

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Pseudomyxoma Peritonei Originating from Transverse Colon Mucinous Adenocarcinoma: A Case Report and Literature Review

Gastroenterology Research and Practice ◽

10.1155/2020/5826214 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Yingbo Gong ◽

Xin Wang ◽

Zhi Zhu

Keyword(s):

Literature Review ◽

Pseudomyxoma Peritonei ◽

Transverse Colon ◽

Mucinous Adenocarcinoma ◽

Lung Metastases ◽

Metastatic Cancer ◽

Genetic Profile ◽

Low Grade ◽

Extensive Literature ◽

Cancer Multiple

Background. Pseudomyxoma peritonei (PMP) is a rare neoplasm involving the peritoneum. Most PMPs are low-grade appendicular mucinous neoplasms (LAMNs). There have been no reports of PMP originating from a transverse colonic mucinous adenocarcinoma and causing metastatic mucinous adenocarcinoma. Case Presentation. We report a 46-year-old woman who presented with a right abdominal mass of more than 4-month duration. Transverse colonic mucinous adenocarcinoma, PMP, and ovarian metastatic mucinous adenocarcinoma were diagnosed. The patient’s diet was normal, and she had no abdominal pain or bloating. The abdomen mass increased in the month before treatment. After chemotherapy, the transverse colon mass and ovarian giant cyst were resected and about 2000 mL of gelatinous tumor tissue was removed. Postoperative histology confirmed PMP from the transverse colonic mucinous adenocarcinoma, ovarian metastatic mucinous adenocarcinoma, and mesocolon metastatic cancer. Multiple lung metastases appeared 8 months after surgery. The patient died 29 months after surgery because of an inability to eat and poor nutrition. A systematic literature review of the management and outcome of all known similar cases is also presented. Conclusions. This is the first report of PMP originating from a transverse colonic mucinous adenocarcinoma. It was diagnosed during resective surgery, involved ovarian metastasis, and survival was short. We did an extensive literature review in order to describe the clinical characteristics, histopathological findings, genetic profile, and potential treatments of PMP caused by nonappendiceal mucinous adenocarcinoma.

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