Serum IGF-I Research Articles

Serum IGF1 Is a Prognostic Marker for Resistance to Targeted Therapies and a Predictive Marker for Anti-IGF1 Receptor Therapy in Melanoma

Serum IGF1 Is a Prognostic Marker for Resistance to Targeted Therapies and a Predictive Marker for Anti-IGF1 Receptor Therapy in Melanoma

Value of serum TGF-β1, IGF-1, MDA and SOD levels in predicting avascular necrosis of femoral head after PRP combined with internal fixation for femoral neck fracture

Value of serum TGF-β1, IGF-1, MDA and SOD levels in predicting avascular necrosis of femoral head after PRP combined with internal fixation for femoral neck fracture

Dietary intake of xylose impacts the transcriptome and proteome of tissues involved in xylose metabolism in swine

Xylose is a primary component of arabinoxylan in swine diets. As arabinoxylan is a significant component of fiber, and fiber is generally rising in practical pig diets globally, the study of arabinoxylan and xylose is of increasing interest. However, the mechanisms by which free xylose may be absorbed and the pathways impacted by xylose have yet to be elucidated in pigs. The objective of this study was to determine the impact of xylose supplementation on gene expression and protein abundance in jejunum, kidney, liver, and muscle tissues which have previously been identified as possible sites of xylose absorption or metabolism. This study aimed to expand the preliminary understanding of dietary xylose metabolism and utilization in pigs. One study, replicated twice with 24 crossbred gilts, was used to assess two dietary treatments: a xylose-free (0%) control and 8% D-xylose. The impact of xylose on growth was monitored by measuring initial and final body weight, serum IGF-1, and liver glycogen concentrations. The rate and efficiency of weight gain were reduced on the xylose diet but not to a level that would occur if xylose was not used at all; the detection of xylose systemically further supports this conclusion. This study confirmed that pigs can utilize dietary xylose. To determine the impact of xylose on tissue metabolism, samples were collected from all four tissues for gene expression analysis by RNA-sequencing, and kidney and liver samples were subjected to proteomic analysis using 2D-DIGE and mass spectrometry. The majority of differentially expressed (DE) genes were identified in the kidney samples (n = 157), with a few identified in the jejunum (n = 16), liver (n = 1), and muscle (n = 20) samples. The DE genes in the kidney were mainly identified as being involved in lipid biosynthesis and fatty acid metabolism. Proteomic results corroborated these findings. Although the inclusion of xylose in a diet at practical levels is shown to impact energy metabolic processes, it has been confirmed that this five-carbon sugar can support levels of growth only slightly below those of glucose, a six-carbon sugar that is more commonly utilized as an energy source in pig diets.

Exercise training modifies the bone and endocrine response to graded reductions in energy availability in skeletally mature female rodents.

Reductions in energy availability leading to weight loss can induce loss of bone and impact important endocrine regulators of bone integrity. We sought to elucidate whether endurance exercise (EX) can mitigate bone loss observed in sedentary (SED) skeletally mature rodents subjected to graded energy deficits. Female virgin rats (n=84, 5-mo-old; 12/group) were randomized to baseline controls and either sedentary (SED) or exercise (EX) conditions, and within each exercise status to adlib-fed (ADLIB), or moderate (MOD) or severe (SEV) energy restriction diets for 12 weeks. Rats assigned to EX groups performed treadmill running to increase weekly energy expenditure by 10%. MOD-ER-SED, SEV-ER-SED, MOD-ER-EX and SEV-ER-EX were fed modified AIN93M diets with 20%, 40% 10%, and 30% less energy content, respectively, with 100% of all other nutrients provided. Energy availability (EA) was effectively reduced by ~14% and ~30% in the MOD-ER and SEV-ER groups, respectively. MOD-ER for 12 weeks resulted in few negative impacts on bone and, except for serum leptin in MOD-ER-SED rats, no significant changes in endocrine factors. By contrast, SEV-ER in SED rats resulted in significantly lower total body and femoral neck bone mass, and reduced serum estradiol, IGF-1 and leptin. EX rats experiencing the same reduction in energy availability as SEV-ER-SED exhibited higher total body mass, lean mass, total BMC, and higher serum IGF-1 at the end of 12 weeks. Bone mechanical properties at 3 bone sites (mid-femur, distal femur, femoral neck) were minimally impacted by ER but positively affected by EX. These findings indicate that combining increased EX energy expenditure with smaller reductions in energy intake to achieve a targeted reduction in EA provides some protection against loss of bone mass and lean mass in skeletally mature female rats, likely due to better preservation of circulating IGF-1, and that bone mechanical integrity is not significantly degraded with either moderate or severe reduced EA.

P-543 Higher maternal age alters the insulin/IGF system and intracellular lipid metabolism of the endometrium and in the preimplantation embryo – insights from the rabbit model.

Abstract Study question Our aim was to analyse the embryo-maternal-interaction, focusing on the insulin/IGF-system and lipid metabolism on day 6 of pregnancy in reproductive young and old rabbits. Summary answer Advanced maternal age has a decisive effect on maternal and embryonic insulin/IGF-signalling and lipid metabolism, leading to higher embryo loss already during preimplantation period. What is known already The reproductive potential in women declines with age. Molecular and biochemical mechanisms involved in age-related infertility and their impact on embryo-maternal-interaction during early pregnancy are still not completely understood. However, establishment of a successful pregnancy depends on the physiological condition of the mother and a continuous dialogue with the developing embryo. The insulin/IGF-system plays a pivotal role in this embryo-maternal crosstalk, connecting maternal insulin/IGF with embryonic metabolism, cell proliferation and differentiation. Study design, size, duration We used the rabbit as reproductive model to investigate maternal age-related alterations in embryo-maternal-interaction during preimplantation period. Compared to humans, the rabbit shares high similarities in early embryo development, gastrulation and lipid metabolism (DOI: 10.1530/REP-12-0091 and DOI: 10.1093/ajcn/62.2.458S). A total of 50 young (16-20 weeks) and 31 old (<108 weeks) sexually mature, female rabbits were used for analysis at day 6 post coitum. Participants/materials, setting, methods We measured mRNA and protein levels of target genes of the insulin/IGF system and lipid metabolism by quantitative PCR, Western Blot and ELISA. Therefore, maternal blood, endometrium and blastocysts were analysed from reproductive young (16 to 20 weeks) and old (over 108 weeks) rabbits on day 6 of pregnancy. Blastocysts and ovulation points were counted and only blastocysts at the pre-gastrulating stage 1, separated in embryoblast (EB) and trophoblast (TB), were used for further analyses. Main results and the role of chance At day 6 of pregnancy, reproductive old rabbits had a lower amount of embryos. Maternal serum insulin and IGF levels were reduced in reproductive old rabbits, accompanied by a paracrine upregulation of IGF1 and its receptors in the endometrium. Preimplantation blastocysts adapted to hormonal changes by reducing IGF1 and IGF2 levels in both embryonic compartments, EB and TB, while the expression of embryonic IGF receptors was unchanged. Furthermore, an increase of fatty acids metabolism was observed in the ageing endometrium, indicated by the higher level of carnitine palmitoyltransferase I B (CPT1B) and elevated expression of fatty acid binding and transport proteins. These results are in line with lower level of fatty acid synthesis (FASN) in the endometrium from old, gravid rabbits, the key enzyme of fatty acid synthesis. Embryonic fatty acid uptake and b-oxidation were increased in EB and TB, too. The observed changes in embryonic and maternal lipid metabolism are caused by the alterations of the transcription factors cAMP-responsive element binding protein (CREB) and peroxisome proliferator-activated receptor (PPAR) α and γ in endometrium and embryos from reproductive old rabbits. Limitations, reasons for caution Rabbit embryogenesis reflects human development only during blastocysts formation. Therefore, statements are limited to the embryogenesis stages investigated. Wider implications of the findings The results of the current study are in accordance with the common literature, showing that advanced maternal age affects developmental competence of embryos. Our study points out that advanced maternal age alters lipid metabolism and insulin/IGF-signalling, which are two crucial components in embryo-maternal-interaction. Trial registration number not applicable

The Ideal Diet for Humans to Sustainably Feed the Growing Population – Review, Meta-Analyses, and Policies for Change

Introduction: As of now, no study has combined research from different sciences to determine the most suitable diet for humans. This issue is urgent due to the predicted population growth, the effect of this on the environment, and the deterioration of human health and associated costs. Methods: A literature review determined whether an optimal diet for humans exists and what such a diet is, followed by six meta-analyses. The standard criteria for conducting meta-analyses of observational studies were followed. A review of literature reporting Hazard Ratios with a 95% confidence interval for red meat intake, dairy intake, plant-based diet, fiber intake, and serum IGF-1 levels were extracted to calculate effect sizes. Results: Results calculated using NCSS software show that high meat consumption increases mortality probability by 18% on average and increases diabetes risk by 50%. Plant-based and high-fiber diets decrease mortality by 15% and 20% respectively (p < .001). Plant-based diets decreased diabetes risk by 27%, and dairy consumption (measured by increased IGF-1 levels) increased cancer probability by 48% (p < 0.01). A vegetarian or Mediterranean diet was not found to decrease the probability of heart disease. A vegetarian diet can be healthy or not, depending on the foods consumed. A Mediterranean diet with high quantities of meat and dairy products will not produce the health effects desired. The main limitations of the study were that observational studies were heterogeneous and limited by potential confounders. Discussion: The literature and meta-analyses point to an optimal diet for humans that has followed our species from the beginnings of humankind. The optimal diet is a whole food, high fiber, low-fat, 90+% plant-based diet. This diet allowed humans to become the most developed species on Earth. To ensure people’s nutritional needs are met healthily and sustainably, governmental dietary interventions are necessary.

Circulating Serum VEGF, IGF-1 and MMP-9 and Expression of Their Genes as Potential Prognostic Markers of Recovery in Post-Stroke Rehabilitation-A Prospective Observational Study.

The key period in post-stroke recovery is the first three months due to the high activity of spontaneous and therapeutic-induced processes related to neuroplasticity, angiogenesis and reperfusion. Therefore, the present study examines the expression of VEGF, IGF-1 and MMP-9 proteins and their genes to identify biomarkers that can prognose brain repair ability and thus estimate the outcome of stroke. It also identifies possible associations with clinical scales, including cognitive assessment and depression scales. The study group comprised 32 patients with moderate ischemic stroke severity, three to four weeks after incident. The results obtained after three-week hospitalization indicate a statistically significant change in clinical parameter estimations, as well as in MMP9 and VEGF protein and mRNA expression, over the rehabilitation process. Our findings indicate that combined MMP9 protein and mRNA expression might be a useful biomarker for cognitive improvement in post-stroke patients, demonstrating 87% sensitivity and 71% specificity (p < 0.0001).

Varying severity COVID-19 effects on the blood indicators of insulin-like growth factors family in patients with nonsmall cell lung cancer

Purpose of the study. An analysis of IGF and their carrying proteins levels in blood serum of patients with non‑small cell lung cancer (NSCLC), depending on the severity of the previous COVID-19 infection.Materials and methods. 60 patients with histologically verified NSCLC T2–3NхM0 receiving treatment at the Thoracic Department (National Medical Research Centre for Oncology, 2020–2021), were included in the study. The control group included 30 NSCLC patients after asymptomatic or mild COVID-19 disease (15 men and 15 women); the main group included 30 (15 men and 15 women) patients after severe or moderate to severe COVID-19. The mean age of patients was 59.11 ± 2.89 years. Blood counts of donors of the same age were used as the norm.Results. The levels of IGF-I, IGF-II, IGFBP2 and IGFBP3 in the blood serum of patients with NSCLC of the main and control groups were higher than those of donors by an average of 2.5, 2.1, 1.7 and 2.7 times, respectively (p &lt; 0.05). The concentration of IGFBP1 was higher in the control group compared to the main group, and decreased in relation to donors: in the control in men and women by 1.4 and 1.9 times, and in the main group by 3.0 and 6.4 times, respectively (p &lt; 0.05). The ratios of IGF and IGFBP1 increased in both groups: IGF-I/IGFBP1 – in the control group from 3.8 to 4.2 times, and in the main group from 7.9 to 14.4 times; IGF-II/IGFBP1 – in the control from 2.4 to 4.5 times, and in the main group from 6.6 to 12.7 times in men and women, respectively (p &lt; 0.05).Conclusions. The level of ligands and almost all of the studied carrier proteins, except for IGFBP1, increases in the blood of patients with NSCLC of both sexes, regardless of the severity of COVID-19. The ratio of IGF-I/IGFBP1 and IGF-II/IGFBP1 in the blood increases in both groups, most significantly in the group with severe and moderate COVID-19, which indicates excessive accumulation of IGF levels and may contribute to a more aggressive course of the malignant process.

Abstract #1406235: Silent Corticotroph Adenomas are More Aggressive than Other Nonfunctional Pituitary Adenomas

Silent corticotroph adenomas (SCAs) are immunopositive for adrenocorticotropic hormone (ACTH) but do not cause Cushing disease. They account for approximately 20% of all corticotroph adenomas and 5% of nonfunctioning pituitary adenomas (NFAs). We present a case of an SCA with extensive invasion outside the sella turcica and causing pathology through mass effect on adjacent structures. A 48-year-old male was found to have a 3.8 cm pituitary mass with invasion of the left cavernous sinus and compression of the optic chiasm during an evaluation of headaches and diplopia. No signs of Cushing syndrome or acromegaly were apparent on examination. Metabolic evaluation was notable for secondary hypothyroidism (TSH 0.7 mIU/L, 0.45-5.33; free T4 0.3 ng/dL, 0.5-1.3) and hypogonadism (LH 2.2 mIU/L, 1.2-8.8; total testosterone 105 ng/dL, 270-1070), though serum prolactin (17.3 ng/mL, 2.6-13.2) and IGF-1 levels (133 ng/mL, 71-224) were unremarkable. ACTH level was increased on multiple measurements (69.9-146.8 μg/dL, 7.2-63.3), but 8 AM cortisol level during an overnight dexamethasone suppression test was only modestly elevated (1.9 μg/dL, expected < 1.8). The patient underwent transsphenoidal surgery (TSS) to remove accessible tumor and relieve symptoms of mass effect. Histopathology was notable for a pituitary adenoma with low Ki-67 proliferation index (< 5%) and 70-80% staining for ACTH. Symptoms recurred approximately 1 y later, and imaging revealed a substantial increase in volume of residual tumor. Unfortunately, the patient died from arterial bleeding during a second attempt at TSS. SCAs are more aggressive than NFAs that fail to stain for an intact pituitary hormone. Patients with SCAs are younger, more likely female, and have a greater likelihood of symptoms at diagnosis than patients with NFAs, though the proportion of SCAs present with extrasellar extension is equivalent to NFAs. SCAs and NFAs progress or recur at the same rate, but time to recurrence for SCAs is more than two-fold faster than for NFAs. Recurrence rate and time to recurrence for SCAs are unaffected by adjuvant radiation. SCAs with extensive staining for ACTH as in this case are more likely to be aggressive than tumors with limited staining for ACTH. Reduced expression of the mismatch repair gene MSH 6/2 may be a driver for the behavior of SCAs. This case illustrates SCAs are a small but challenging subset of NFAs with greater propensity to cause symptoms of mass effect and recur quickly than the typical NFA. Extensive ACTH staining is a poor prognostic sign for tumor recurrence.

Abstract #1407325: Acromegalic Arthropathy Masquerading as Rheumatoid Arthritis- A Diagnostic Challenge

Acromegaly is a disorder related to the excessive production of growth hormone after puberty. The estimated incidence of acromegaly is approximately 3/10,00,000 persons per year. Although figures in the literature vary, the diagnosis of acromegaly is often delayed by 7-10 years from the onset of symptoms. Increased provider recognition allows for early diagnosis and treatment, which may prevent long-term complications of acromegaly. This case highlights the importance of increased provider awareness of the condition, and its clinical features. A 50-year-old female presented to primary care with several years of progressive joint pain in the hands with associated swelling and morning stiffness. On examination, she had synovitis in her PIP and MCP joints. Ultrasound of her hands revealed diffuse synovial fluid complexes and tenosynovitis. She was referred to Rheumatology and was diagnosed with seronegative rheumatoid arthritis. She was trialed on MTX, HCQ, and SSZ, followed by several biologics (Adalimumab, Etanercept, Abatacept) without clinical improvement. This prompted re-evaluation of her diagnosis. The rheumatologist recognized clinical features suggestive of acromegaly- mild frontal bossing, enlarged hands and dactylitis. A serum IGF1 level was elevated, which was confirmed on repeat testing upon establishing care with Endocrinology. MRI brain revealed a 7 mm pituitary microadenoma. The patient has been referred to neurosurgery and is awaiting surgical intervention. The clinical manifestations of acromegaly include frontal bone bossing, jaw prognathism, acral overgrowth, osteoarthritis, diabetes mellitus, hypertension, respiratory and cardiac failure. With untreated, prolonged disease, concentric myocardial hypertrophy develops, and diastolic heart failure occurs, which are not reversible. Skeletal disorders cause significant functional disability and compromised quality of life in patients with acromegaly. 70% of such patients have large-joint and axial arthropathy that includes thickened articular cartilage, periarticular calcifications, osteophyte overgrowth, and synovitis. About 40% of cases are initially diagnosed by an internist, and the rest are diagnosed when patients are seen by ophthalmologists for visual disturbances, by dental surgeons for bite disorders, by gynecologists for menstrual dysfunction and infertility, by rheumatologists for osteoarthritis, or by sleep-disorder specialists for obstructive sleep apnea. In conclusion, high suspicion of the diagnosis, along with early diagnosis, is critical in possibly preventing the morbidity associated with acromegaly and improving long-term outcomes.

The influence of interventional measures on metabolic factors in fluoride and aluminum combined poisoning bones

ABSTRACT This study aimed to evaluate the effects of soybean, selenium and spirulina on bone metabolic factors in rats with combined fluoride and aluminum poisoning.Methods:Sixty SD rats were allocated to five groups: A control group, a high-fluoride aluminum group, a high-fluoride aluminum plus soybean group, a high-fluoride aluminum plus selenium group, and a high-fluoride aluminum plus spirulina group. Serum samples were collected and radioimmunoassay (RIA) was used to measure osteocalcin (BGP), calcitonin (CT), parathyroid hormone (PHT) and insulin growth factor I (IGF-1) levels after 90 and 165 days of intervention. 1. When comparing the serum BGP level in the high-fluorine aluminum plus selenium group with the high-fluorine aluminum group, suggesting that the addition of selenium intervention was beneficial in reducing the effect of high-fluorine aluminum on bone homeostasis. 2. After 90 days and 165 days, the difference in serum CT levels between the intervention group and the control group was not statistically significant, suggesting an effect of the intervention factors.3. After 90 days of exposure, the three intervention groups had lower serum PTH levels (p < 0.00), inferring the efficacy of the interventions.4. After 90 days, serum IGF-1 levels were elevated in the Spirulina group compared with the high-fluorinated aluminum group, and the difference was statistically significant, suggesting that the addition of Spirulina intervention may counteract the inhibition of bone growth by high-fluorinated aluminum. The intervention of soybean, selenium, and spirulina can counterbalance the effects of fluoride and aluminum on bone metabolism and slow down the process of bone turnover.

Phase 1 Safety and Pharmacodynamic Results of VRDN-001, a Full Antagonist Antibody to the Insulin-Like Growth Factor-1 Receptor (IGF-1R) in Development for Thyroid Eye Disease (TED) (P3-9.007)

<h3>Objective:</h3> Report the interim safety and pharmacodynamic (PD) results for healthy volunteers from a phase 1/2 clinical trial (NCT05176639) evaluating VRDN-001 intravenously administered at 3–20 mg/kg. <h3>Background:</h3> Clinical and preclinical studies have confirmed insulin-like growth factor-1 receptor (IGF-1R) antagonism can reduce the inflammation and proptosis that occur in Thyroid Eye Disease (TED). VRDN-001, a full antagonist antibody to the IGF-1R, is under development for the treatment of TED. <h3>Design/Methods:</h3> Adult healthy volunteers were randomized 3:1 to receive 2 intravenous infusions 3 weeks apart of either placebo or 3, 10, or 20 mg/kg VRDN-001. PD parameters (IGF-1 serum levels) and adverse events (AEs) were assessed up to 50 days. <h3>Results:</h3> Thirteen participants received VRDN-001 3 mg/kg (n=3), 10 mg/kg (n=3), 20 mg/kg (n=4), or placebo (n=3). Mean age was 49 years (range: 25–73) and 5 were female. All VRDN-001 doses elicited rapid, sustained, and similar increases in IGF-1 serum levels, a biomarker for IGF-1R inhibition. Following the first infusion, IGF-1 increased within a day, reaching 3–5-fold above baseline by Day 8. Increases were sustained until the second infusion, and then further increased to 5–7-fold above baseline (&gt;500 ng/mL), and sustained through Day 50. No increases in serum IGF-1 occurred for placebo. Eleven of the 13 participants experienced 19 AEs (16 mild and 3 moderate). Transient hypotension (10 mg/kg group) and muscle spasm (placebo group) were the only AEs to be deemed treatment-related by the masked investigator. No treatment-related hyperglycemia or hearing impairment was observed. <h3>Conclusions:</h3> VRDN-001 administered to healthy volunteers at 3–20 mg/kg indicated maximal target engagement at all doses and was generally safe and well-tolerated, with no observed treatment-related hyperglycemia or hearing impairment. Results from the ongoing evaluation of VRDN-001 dosed at 3–20 mg/kg in TED patients will further inform potential treatment regimens. <b>Disclosure:</b> Dr. She has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. She has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Dianthus Therapeutics. Dr. She has stock in Viridian Therapeutics. Dr. Katz has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. Katz has received stock or an ownership interest from Viridian Therapeutics. Mrs. Summerfelt has received personal compensation for serving as an employee of Viridian Therapeutics. An immediate family member of Mrs. Summerfelt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Viridian Therapeutics. Mrs. Summerfelt has stock in Viridian Therapeutics. Dr. Oshaughnessy has received personal compensation for serving as an employee of viridian therapeutics. Dr. Oshaughnessy has stock in viridian therapeutics. Mr. Dickinson has nothing to disclose. Dr. Foster has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. Bedian has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. Bedian has received personal compensation for serving as an employee of Dianthus Therapeutics. Dr. Bedian has stock in Viridian Therapeutics. Dr. Bedian has stock in Astria Therapeutics.

Lower serum insulin-like growth factor 1 concentrations in patients with chronic insomnia disorder.

Insulin-like growth factor 1 (IGF-1) is a crucial neurotrophin that is produced in the brain and periphery and may play an important role in insomnia and mood disorders. We aimed to analyze its serum concentrations in patients with chronic insomnia disorder (CID). Patients with CID were enrolled in this study and divided into the CID group [Generalized Anxiety Disorder-7 (GAD-7) score < 10] and the CID with anxiety group (GAD-7 score ≥ 10). Age-and sex-matched healthy volunteers were recruited as controls. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality and the GAD-7 and the Patient Health Questionnaire-9 to assess emotional status. All subjects were monitored via polysomnography, and the serum IGF-1 concentrations in their peripheral blood were detected via enzyme-linked immunosorbent assays. We enrolled 65 patients with CID (of whom 35 had anxiety) and 36 controls. The PSQI score and IGF-1 concentration in the CID and CID with anxiety groups were higher than those in the control group. The apparent difference in IGF-1 concentration between the CID and CID with anxiety groups was not statistically significant. The IGF-1 concentration in patients with CID was linearly correlated with the GAD-7 score, PSQI score, and stage 3 non-rapid eye movement (stage N3) time. The serum IGF-1 concentration in patients with CID was lower than that of participants without CID, negatively correlated with anxiety score and sleep quality, and positively correlated with stage N3 time.

Abstract 2099: Predicting the metastatic potential in breast cancer patients in Bangladesh

Abstract Background and Aims: Breast cancer (BC) is the leading cause of mortality among all cancers in Bangladeshi women. The prognosis of metastatic breast cancer depends on certain factors, like surgery, radiotherapy, chemotherapy, hormonal receptor content of the tumor or associated illness such as diabetes mellitus and obesity. Among the associated illness, diabetes mellitus is one of the most common metabolic disease worldwide, which is linked to an increased risk of developing breast cancer and an even higher risk of recurrence and dying from this disease. In this context, we studied diabetic and metabolic disease related growth and metabolic factors in breast cancer patients for assessing the prognosis of BC. Methods: A total of 180 mastectomy patients were purposively taken in the present study. Data were collected from retrospective information. Anthropometric and biochemical parameters were taken by standard methods. Growth and metabolic factors were determined by enzyme-linked immunosorbent assay (ELISA) method. Association of diabetes treatment modalities with breast cancer metastasis was evaluated by correlation analysis among 80 diabetic patients. Results: Serum level of insulin-like growth factor 1 (IGF1) was found to be significantly higher (p=0.001) in ER and PR negative breast cancer than their positive counterparts. Patients who had lymph node positive and Her2 borderline showed a significant reduction in serum adiponectin level (p&amp;lt;0.05) and this association was retained after adjusting the confounding variables. Furthermore, delayed treatment, IGF-1, ALP, sleeping hours were significant predictors for metastasis of breast cancer patients in Bangladesh. The Diabetic BC patients treated with both insulin and oral drug was found to be negatively associated with breast cancer metastasis compared to Diabetic-BC patients treated with only oral drugs (p&amp;lt;0.05). However, BC metastasis did not any have an association with serum fasting insulin or insulin resistance. Obesity also did not show any relation with BC prognosis. Conclusions: Serum IGF-1 and adiponectin may have an association with invasiveness and metastasis of breast cancer. Diabetes treatment with combination therapy ameliorates breast cancer metastasis.Breast cancer prognosis would be independently predict by serum levels of IGF-1 as well as IGF1 could be used as a screening biomarker when validated in a larger sample size. Citation Format: Salima Akter, Muhammad Saiedullah, Mousumi Bhowmik, Hajara Akhter, Shahina Ansary, Waheed Akhtar, Sufi Hannan Zulfiqur Rahman, Tae Gyu Choi, Sung Soo Kim. Predicting the metastatic potential in breast cancer patients in Bangladesh [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2099.

Exercise combined with lysine-inositol vitamin B12 promotes height growth in children with idiopathic short stature

ObjectiveThis study was aimed to systematically determine the effect of exercise combined with lysine-inositol vitamin B12 (VB12) therapy on the height of children with idiopathic short stature (ISS). MethodsSixty children with ISS were randomly divided into observation and control groups (N = 30). Each group was given lysine-inositol VB12 oral solution (10 mL bid). Simultaneously, the observation group exercised following the “ISS exercise instruction sheet”. The height (H), growth velocity (GV), height standard deviation score (HtSDS) and other indicators were compared after 6 and 12 months of intervention, respectively. After 12 months of intervention, the biochemical indicators of the two groups, together with the correlation between the average days of exercise per week and average minutes of exercise per day, GV and serum growth hormone were analyzed. ResultsAfter 6 and 12 months of treatment, the GV, serum GHRH, GHBP, GH, IGF-1, and IGFBP-3 levels in the observation group were significantly higher than those in the control group, and HtSDS was significantly lower than that in the control group (P<0.01). After 12 months of treatment, the height of the observation group was significantly higher than that of the control group (P<0.05). There was no significant difference in the biochemical indicators between two groups (P>0.05). Average days of exercise per week and average minutes of exercise per day were positively correlated with GV and GHBP levels. Serum GHRH, GH, IGF-1, and IGFBP-3 levels were negatively correlated. Average minutes of exercise per day were negatively correlated with GV and GHBP levels. Serum GHRH, GH, IGF-1, and IGFBP-3 levels were positively correlated. ConclusionRegular and moderate stretching exercises combined with lysine-inositol VB12 can effectively promote height growth of children with ISS, which is clinically safe. The mechanism promotes serum GHRH, GHBP, GH, IGF-1, and IGFBP-3 levels.

The impact of specific balneotherapy on the endocrine physio-pathological mechanism in obesity

Obesity is a complex, multifactorial metabolic pathology, within the path of modification of the endocrine system plays a significant role. Changes in growth hormone (GH) and in-sulin growth factor (IGF) have been associated with obesity in various ways, mainly through changes in GH-binding proteins, insulin and ghrelin levels. The balneal treat-ment with Techirghiol Romanian sapropelic mud has an important impact on the endo-crine system, primarily through the action on the hypothalamic-pituitary-adrenal axis. We investigated the secretory changes of the IGF-1 hormone that appeared after the balne-al treatment. It was a total number of 52 patients, divided into two groups: 1 group who performed the treatment with Techirghiol sapropelic mud at thermoneutrality tempera-tures - warm mud baths, and the second group who followed treatment with the balneal therapeutic factor in a thermal contrast regime - cold mud baths. We studied whether there are correlations between the body mass index (BMI) and the secretion of this hor-mone. We also determined the serum levels of blood glucose at admission and discharge. In the cold mud baths- thermal contrast therapy, can be observed a statistically significant increase in IGF-1 values during the balneal treatment (p = 0.044 &lt; α = 0.05). Comparative-ly, in the warm mud baths, the increase in serum IGF-1 reached values close to statistical significance at the end of the treatment (p = 0.067 &gt; α = 0.05). There were no statistically significant correlations between BMI and IGF-1 hormone secretion at admission and at discharge. The results showed a statistically significant decrease in blood glucose values determined at admission and discharge in the group that performed warm mud baths. The balneal treatment with sapropelic mud of Techirghiol lake, from Romania, through the impact on the endocrine system, on the hypothalamic-pituitary-adrenal axis, can be registered as a treatment with a natural therapeutic factor with an impact on obesity, ther-apy carried out within the parameters of metabolic safety, and the conduct of future re-search in this direction it will help develop new concepts and approaches to obesity.

Hepatitis C Virus and Hepatitis C Virus-Associated Hepatocellular Carcinoma in Egyptian Patients: Driving Disease Progression

Background: Hepatocellular carcinoma is the leading cause of cancer-related death worldwide and it is commonly associated with hepatitis C virus infection. Identifying the key mechanisms and biological markers involved in the hepatitis C virus-associated hepatocellular carcinoma may help in early detection and/or diagnosis of this malignancy. The aim of this study was to evaluate and assess the role of the serum VEGF, NF-kB, and IGF-1 in incidence and development of hepatocellular carcinoma in hepatitis C virus-infected patients. Methods and Results: VEGF, NF-kB, and IGF-1 were measured by ELISA assay in Egyptian patients with hepatitis C virus infection and hepatocellular carcinoma-associated hepatitis C virus infection, healthy individuals. Serum VEGF, NF-kB, and IGF-1 were significantly elevated in HCV and hepatitis C virus-associated hepatocellular carcinoma patients compared to the control group. Additionally patient with hepatitis C virus-associated hepatocellular carcinoma showed significantly higher serum levels of NF-kB, and IGF-1 compared with hepatitis C virus infection patients. Conclusions: Our data supports the role of VEGF, NF-kB, and IGF-1 in development of hepatocellular carcinoma during the course of hepatitis C virus infection and the use of these biomarkers in combination with alpha-fetoprotein (AFP) may offer an improved diagnostic tool for hepatocellular carcinoma early detection.

Autonomous growth hormone secretion due to McCune Albright syndrome in paediatric age group: an ominous triad.

The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to elucidate challenges and intricacies in its diagnosis and management. It was a single centre study carried out in individuals with MAS and autonomous GH secretion (AGHS). In addition, a systematic search of literature across three databases (PubMed, Scopus and EMBASE) was performed from inception until May 31, 2021 to identify cases of MAS with AGHS in the pediatric age group (<18 years). Three cases from authors centre and 42 cases identified from systematic literature review were analysed. Precocious puberty was the most common presenting endocrinopathy seen in 56.8% (25/44) cases, followed by hyperthyroidism (10/45), hypophosphatemia (4/45), and hypercortisolism (2/45). Cranio-facial fibrous dysplasia (CFFD) was seen in all while polyostotic fibrous dysplasia and Café au lait macule was seen in 40/45 (88.9%) and 35/45 (77.8%), respectively. Pituitary adenoma (58.3% microadenoma) was localized in 53.3% (24/45) cases on pituitary imaging. Biochemical and clinical remission of AGHS was achieved in 61.5% (24/45) cases with medical therapy. Diagnosing AGHS in MAS is challenging because of concomitant presence of CFFD, non-GH endocrinopathies associated height spurt and elevated serum IGF-1. GH-GTT should be performed in presence of elevated growth velocity and serum IGF-1 (>1 X ULN) despite adequate control of non-GH endocrinopathies. Medical management can lead to disease control in substantial number of cases and often entails use of multiple agents.

Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model.

This study aimed to explore the effects of osteogenic growth peptide C-terminal pentapeptide (G36G), and its analog G48A on bone modeling in rats with ovariectomy-induced osteoporosis. Ovariectomized rats were administered PBS (OVX group), risedronate (RISE group), G36G combined with risedronate (36GRI group), G36G (G36G group), or G48A (G48A group). The sham-operation rats (SHAM group) were administered PBS. Serum osteocalcin and IGF-2 levels in the SHAM, OVX, G36G, G48A, and RISE groups were observably lower than the 36GRI group (P < 0.01) and the bone mineral density of the entire femur, distal metaphysis, and lumbar L1-L4 in the 36GRI group were notably increased (P < 0.05). The bending energy of the 36GRI group was prominently higher than the other groups (P < 0.05). Other features measured in the study that provided significant outcomes was the ratio of femora ash weight/dry weigh, parameters of trabecular bone volume (TBV)/total tissue volume, TBV/sponge bone volume, mean trabecular plate thickness, mean trabecular plate space, bone surface, parameters of sfract(s) and sfract(d), tetracycline-labeled, and osteoid surfaces. Bone loss in ovariectomized rats may be partially inhibited by G36G and G48A. A combination treatment with G36G and risedronate may be an effective intervention for osteoporosis.

Association between pain, arthropathy and health-related quality of life in patients suffering from acromegaly. A cross-sectional study

Despite successful therapy, acromegalic patients have reduced health-related quality of life (HRQoL) compared to healthy controls. Finding predictors of poor HRQoL can be crucial to improving these patients' global health state. Aim: The primary objective of the study was to find out predictors of HRQoL. Secondary objectives were: (I) to determine correlations with AcroQoL subscales, and (II) to identify predictors for subscales. In this cross-sectional study conducted in 2019 at the Messina Policlinic Hospital, 45 acromegalic patients were assessed at the Physical and Rehabilitative Medicine Ambulatory. During routine outpatient clinic attendances, the following questionnaires were administered: Acromegaly Quality of Life Questionnaire (AcroQoL), Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), and Western Ontario and McMaster Universities Arthritis Index (WOMAC). We furthermore included the following variables obtained by medical record review: age, BMI, disease duration, previous surgery (Yes/No), previous radiotherapy (Yes/No), use of GH lowering medications (Yes/No), hypertension (Yes/No), diabetes mellitus (Yes/No), and biochemical control of the disease (Yes/No): immunoradiometric assays were employed to serum GH and IGF-1 measurements to identify biochemical control of the disease. Correlation between outcome measures and AcroQoL has been performed. Pearson's r was calculated for continuous data following normal distribution (AcroQoL, PASQ, AcroQoL-B, AcroQoL-R, WOMAC-P), while Spearman's rank order correlation was calculated for non-normally distributed data (WOMAC, WOMAC-F, WOMAC-S, AcroQoL-P) and point-biserial correlation for binary variables (biochemically controlled disease, use of GH lowering medications, radiotherapy, surgery). The same correlation analysis was performed for the AcroQoL subscales. Multiple linear regression with backwards, stepwise analysis was used to assess the influence on AcroQoL of correlated variables. AcroQoL was strongly negatively correlated with PASQ (r=-0.700, p<0.001) and negatively correlated with WOMAC [rs (43)=-0.530, p<0.001] and among WOMAC subscales with WOMAC-Physical fitness [rs (43)=-0.518, p<0.001] WOMAC-Pain [r (43)=-0.428, p=0.003], WOMAC-Stiffness [rs (43)=-0.393, p=0.007], and radiotherapy [r (43) =-0.314, p=0.035]. After univariate stepwise regression, PASQ was the strongest independent predictor of AcroQoL, with R2 of 0.392 [F (1,43)=27.695, p<0.001]. This study shows that the severity of painful symptoms is the most important predictor of HRQoL in patients with acromegaly; at the same time, acromegalic arthropathy leads to pain and to a variable amount of functional impairment, exerting great impact on the patient's perception of his health status. Measure of the progression of arthropathy and symptomatic management could lead to a great HRQoL benefit.