Hyperhomocysteinemia and Associated Biological Markers in a Congolese Population of Type 2 Diabetes Mellitus in Brazzaville

The search for new biomarkers predictive of type 2 diabetes currently constitutes a research avenue in Bioclinical. Total homocysteine remains a preferred target due to its involvement in the occurrence of degenerative complications in type 2 diabetics. The aim of this work was to study hyperhomocysteinemia and other biochemical markers associated with T2D in the Congolese population. This was an analytical case-control study carried out between October 2022 and October 2023. The study population consisted of 150 subjects including 100 T2D patients and 50 control subjects. The main clinical data were collected on a pre-established form. Homocysteine determination was carried out by the sandwich ELISA method. The other biochemical markers were measured by colorimetric enzymatic methods. Hyperhomocysteinemia was present in 27.3% (41/150) of the entire study population. Type 2 diabetics had a frequency of hyperhomocysteinemia of 36% (36/100) and control 10% (5/50) (p = 0.001). The mean hyperhomocysteinemia concentration was 31.9 μmol/l with extremes ranging from 18 to 103 μmol/l. Means of biological markers between diabetics and controls showed a statistically significant difference (p = 0.01). The risk factors associated with this HHcy were: sex (OR = 3.5), age (OR = 9.4), sedentary lifestyle (OR = 3.4) and glycosylated hemoglobin (OR = 12) with a p-value <0.05 respectively. Our results suggest that hyperhomocysteinemia can be considered as a predictive biomarker in the bioclinic of Congolese type 2 diabetic patients.

Magnetic Resonance Imaging and Biological Markers in Pituitary Adenomas with Invasion of the Cavernous Sinus Space

Objective: To investigate the predictability of MRI and the possiblebiological markers of cavernous sinus invasion of pituitary adenomas associated with fourphenomenas: angiogenesis, cell proliferation, apoptosis and matrix metalloproteinase. Methods: Weevaluated 45 patients with pituitary adenoma according to the MRI, surgical findings and theimmunohistochemistry staining of tumor tissues. Results: The results have shown that the sensitivityof MRI for predicting cavernous sinus invasion in this prospective study was 60%, its specificity85%, its positive predictive value 83.33%, negative predictive value 62.96%. 45 specimens ofpituitary adenomas were analyzed for expression of F8, VEGF, Ki-67, c-myc, Bcl-2, nm23 and MMP-9immunoreactivity using immunoperoxidase staining. MVD was assessed using F8-related antigen. Theresults have shown that MVD of invasive pituitary adenomas was significantly higher than that ofnoninvasive (P 【 0.001). There was an association between the invasion of pituitary adenomas andKi-67 LI (P = 0.039) or the expression of VEGF (P 【 0.001) and MMP-9 (P 【 0.001). But c-myc LI andBcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 versus P =0.201). On the other hand, there is an inverse relationship between nm23 expression and tumorinvasion (P 【 0.001). Conclusion: Parasellar extension of pituitary adenomas through the medial wallof the cavernous sinus is diagnosed at surgery, and with sensitive gadolinium-enhanced MRI, itsextent can be partly determined by radiology. Although our study has shown that MVD and theexpression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas,they are lack of specificity. These markers can only provide some useful information.

Urinary nucleosides as biological markers for patients with colorectal cancer

AIM: Fourteen urinary nucleosides, primary degradation products of tRNA, were evaluated to know the potential as biological markers for patients with colorectal cancer. METHODS: The concentrations of 14 kinds of urinary nucleosides from 52 patients with colorectal cancer, 10 patients with intestinal villous adenoma and 60 healthy adults were determined by column switching high performance liquid chromatography method. RESULTS: The mean levels of 12 kinds of urinary nucleosides (except uridine and guanosine) in the patients with colorectal cancer were significantly higher than those in patients with intestinal villous adenoma or the healthy adults. Using the levels of 14 kinds of urinary nucleosides as the data vectors for principal component analysis, 71% (37/52) patients with colorectal cancer were correctly classified from healthy adults, in which the identification rate was much higher than that of CEA method (29%). Only 10% (1/10) of patients with intestinal villous adenoma were indistinguishable from patients with colorectal cancer. The levels of m1G, Pseu and m1A were positively related with tumor size and Duke's stages of colorectal cancer. When monitoring the changes in urinary nucieoside concentrations of patients with colorectal cancer associated with surgery, it was found that the overall correlations with clinical assessment were 84% (27/32) and 91% (10/11) in response group and progressive group, respectively. CONCLUSION: These findings indicate that urinary nucleosides determined by column switching high performance liquid chromatography method may be useful as biological markers for colorectal cancer.

Combined measurement of serum tumor markers in patients with hepatocellular carcinoma

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The Expression of Estrogen Receptor Subtypes in Prolactinomas and Their Relationship to Tumor Biological Behavior

Dopamine agonists （DA） are a first-line therapy for prolactinomas （PA）. However, nearly 10% of prolactinomas do not respond to DA therapy. A considerable number of studies have shown that estrogen plays an important role in the development of prolactinomas. However, the expression of estrogen receptors （ER） in prolactinomas has not been fully explored. Accordingly, we examined the levels of ESR1 and its subtypes A5-DeI-ESR1 and ESR2 mRNA in prolactinomas. In the present study,

BIOLOGICAL MARKER OF MIDDLE JURASSIC OIL SHALE SEQUENCE FROM SHUANGHUI AREA,NORTHERN TIBETAN PLATEAU

The oil shale with marine origin was first reported in 1987 from Shuanghui of the Qiangtang region. Its depositional sequence consists of brown\|black oil shale interbedded massive to thin limestone. Eleven oil shale beds occur and aggregated thickness is up to 47 38m. It deposit age is confined in middle Jurassic by fossils identification. Nine samples selected from horizons with high\|organic contents have been examined by organic geochemistry approach. The oil\|shale range widely in organic carbon content (Toc), average in 8 34%, maximum values reaching 26.12%. Toc are markedly varied in vertical section. The Upper and lower members are slightly low and increase in the middle. The oil\|shale sediments are characterized by high concentration in chloroform bitumen“A”(608～18707)×10 -6 )and total hydrocarbon ((311～5272)×10 -6 ).The Rock\|Eval T \|max data (434～440℃) and vitrinite reflectance values (0.88%～1.26%) indicate that oil\|shale sequence are mature in all samples. The organic matter is predominantly made up of typeⅡ kerogen.

Monitoring of Biological Responses of Tumor Cells after Irradiation with ^(99m)Tc-MIBI——An In Vitro Study

To explore the possibility to employ 99m Tc MIBI to monitor biological response of tumor cells after irradiation and to observe the relation between the radiation doses and the uptake levels of 99m Tc MIBI in tumor cells, the cells were irradiated with a single dose of 2 Gy, 10 Gy and 20 Gy respectively. The uptake of 99m Tc MIBI in each dosage group was determined before and 24, 48, 72 h after irradiation respectively. Apoptosis index , plating efficiency of tumor cells was simultaneously determined. There was a positive correlation between uptake levels of 99m Tc MIBI and AI. A negative correlation was noted between the uptake levels and PE . It is suggested that 99m Tc MIBI may be used as a tracer to monitor the change of viability state of tumor cells after being irradiated with different doses.

An Overview on Biological Markers in Reproductive and Developmental Toxicology: Concepts, Definitions and Use in Risk Assessment

Reproduction and development are complex couple-dependent processes. Risk assessment for these health outcomes requires the use of biomarkers to link exposures to disease. Biological markers of susceptability, external dose, internal dose, biologically effective dose, early or late biological responses, altered reproductive or developmental function, and reproductive or developmental disease are introduced. Using these biomarkers it is possible to define a biologically based risk assessment methodology for reproductive and developmental toxicity. Risk assessment for reproductive toxicity requires definition of male and female fecundity, couple-specific factors, spontaneous abortion, rate, and other factors. Using using sperm count as a biomarker for male fecundity, an example of a reproductive risk assessment using biomarkers is performed.

Biological Markers on Human Pregnancy

This article reviews a selected set of recently described pregnancy-associated proteins which possess potential for both signaling pregnancy onset and monitoring its course. These molecules are compared and contrasted with human chorionic gonadotropin, the first pregnancy-associated protein to be discovered, and the standard biomarker of pregnancy to which all others must still be referenced. Recent advances in hCG research have focused on the structural determination and diagnostic significance of the subunits and fragments of the hCG molecule, particularly in urine. An outline of the potential utility of this approach is also presented.

Effects of VEP neoadjuvant chemotherapy before esophageal cancer surgery on the malignant biological behaviors of tumor cells

Objective: To study the effects of VEP neoadjuvant chemotherapy before esophageal cancer surgery on the malignant biological behaviors of tumor cells. Methods: Patients who were diagnosed with locally advanced esophageal cancer in Dangyang People's Hospital between March 2015 and March 2017 were selected as the research objects and randomly divided into the VEP group who received preoperative VEP (etoposide + 5-fluorouracil + cisplatin) chemotherapy and the control group who accepted routine preoperative preparation. The serum contents of tumor markers were determined at diagnosis and 1 d before surgery;the expression of proliferation genes and invasion genes in tumor tissue were determined after surgical resection. Results: One day before surgery, serum CEA, CA125, CYFRA21-1 and SCC-Ag levels of VEP group were significantly lower than those at diagnosis, and serum CEA, CA125, CYFRA21-1 and SCC-Ag levels of control group were not significantly different from those at diagnosis;after surgical resection, PTEN, Smac and PTPN14 mRNA expressions in the tumor tissue of VEP group were significantly higher than those of control group whereas CyclinB1, CDK1, Grp94, MMP2, β-catenin, Slug, Vimentin and N-cadherin mRNA expressions were significantly lower than those of control group. Conclusions: VEP neoadjuvant chemotherapy before esophageal cancer surgery can reduce the growth of tumor cells and inhibit the proliferation and invasion of tumor cells in the lesion.

Relationship between phenotypes of cell-function differentiation and pathobiological behavior of gastric carcinomas

AIM: To reveal the correlation between the functional differentiation phenotypes of gastric carcinoma cells and the invasion and metastasis by a new way of cell-function classification.METHODS:Surgically resected specimens of 361 gastric carcinomas(GC) were investigated with enzyme-, mucin-, and tumor-related marker immunohistochemistry. According to the direction of cell-function differentiation, stomach carcinomas were divided into five functionally differentiated types. RESULTS: (1) Absorptive function differentiation type (AFDT): there were 82 (22.7%) patients including 76 (92.7%) aged 45 years. Sixty-nine (84.1%) cases belonged to the intestinal type. Thirty-eight (46.3%) expressed CD44v6 and 9 (13.6%) of 66 male patients developed liver metastasis.The 5-year survival rate of patients in this group (58.5%) was higher than those with the other types (P【0.01). (2) Mucin secreting function differentiation type (MSFDT): 54 (15%) cases. Fifty-three (98.1%) tumors had penetrated the serosa, 12 (22.2%) expressed ER and 22 (40.7%) expressed CD44v6. The postoperative 5-year survival rate was 28.6%. (3) Absorptive and mucin-producing function differentiation type (AMPFDT): there were 180 (49.9%) cases, including 31 (17.2%) aged younger than 45 years. The tumor was more common in women (62, 34.4%,) and expressed more frequently estrogen receptors (ER) (129, 81.7%) than other types (P【0.01). Ovary metastasis was found in 12 (19.4%) out of 62 female subjects. The patients with this type GC had the lowest 5-year survival rate (24.7%) among all types. (4) Specific function differentiation type (SFDT): 13 (3.6%) cases. Nine (69.2%) tumors of this type derived from APUD system, the other 4 (30.7%) were of different histological differentiation. Sixty per cent of the patients survived at least five years. (5) Non-function differentiation type (NFDT): 32 (8.9%) cases. Nineteen (59.4%) cases had lymph node metastases but no one with liver or ovary metastasis. The 5-year survival rate was 28.1%. CONCLUSION: This new cell-function classification of GC is helpful in indicating the characteristics of invasion and metastasis of GC with different cell-function differentiation phenotypes. Further study is needed to disclose the correlation between the cell-functional differentiation phenotypes and the relevant genotypes and the biological behavior of gastric carcinoma.

Spinal cord biological safety of image-guided radiation therapy versus conventional radiation therapy

Tumor models were simulated in purebred Beagles at the T9-10 levels of the spinal cord and treated with spinal image-guided radiation therapy or conventional radiation therapy with 50 or 70 Gy total radiation. Three months after radiation, neuronal injury at the T9-10 levels was observed, including reversible injury induced by spinal image-guided radiation therapy and apoptosis induced by conventional radiation therapy. The number of apoptotic cells and expression of the proapoptotic protein Fas were significantly reduced, but expression of the anti-apoptotic protein heat shock protein 70 was significantly increased after image-guided radiation therapy compared with the conventional method of the same radiation dose. Moreover, the spinal cord cell apoptotic index positively correlated with the ratio of Fas/heat shock protein 70. These findings indicate that 3 months of radiation therapy can induce a late response in the spinal cord to radiation therapy; image-guided radiation therapy is safer and results in less neuronal injury compared with conventional radiation therapy.

Evaluation of treatment response for breast cancer:are we entering the era of "biological complete remission"?

Breast cancer is one of the most common malignancies in women. The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality. In this study, we tried to explore the role of circulating tumor cell （CTC） detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer; meanwhile, we attempted to assess the concept of ＂biological complete remission＂ （bCR） in this regard. A 56-year-old patient with breast cancer （T2N1M1, stage IV left breast cancer, with metastasis to axillary lymph nodes and lungs） received 6 cycles of salvage treatment with albumin-bound paditaxd plus eapecitaabine and trastuzumah. Then, she underwent CTC detection and PET/CT for efficacy evaluation. CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer. The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological （pathological） complete remission. The integrated application of the concepts including bCR, imageological CR, and histological CR can achieve the early and prognosis of breast cancer. accurate assessment of biological therapeutic reponse and

Hepatoma cell line HepG2.2.15 demonstrates distinct biological features compared with parental HepG2

AIM:To investigate the biological features of hepatitis B virus(HBV)-transfected HepG2.2.15 cells. METHODS:The cell ultrastructure,cell cycle and apoptosis,and the abilities of proliferation and invasion of HBV-transfected HepG2.2.15 and the parent HepG2 cells were examined by electron microscopy,flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trans-well assay.Oncogenicity of the two cell lines was compared via subcutaneous injection and orthotopic injection or implantation in nude mice,and the pathological analysis of tumor formation was performed.Two cytoskeletal proteins were detected by Western blotting. RESULTS:Compared with HepG2 cells,HepG2.2.15 cells showed organelle degeneration and filopodia disappearance under electron microscope.HepG2.2.15 cells proliferated and migrated slowly in vitro,and hardly formed tumor and lung metastasis in nude mice.Flow cytometry showed that the majority of HepG2.2.15 cells were arrested in G1 phase,and apoptosis was minor in both cell lines.Furthermore,the levels of cytoskeletal proteins F-actin and Ezrin were decreased in HepG2.2.15 cells. CONCLUSION:HepG2.2.15 cells demonstrated a lower proliferation and invasion ability than the HepG2 cells due to HBV transfection.

Risk of infections associated with biological treatment in inflammatory bowel disease

Tumor necrosis factor-&#x003b1; (TNF-&#x003b1;) inhibitors are biological agents introduced in the late 1990s for the treatment of different immune-mediated diseases as inflammatory bowel disease, rheumatoid arthritis and psoriasis. The most commonly used TNF-&#x003b1; antagonists are infliximab, adalimumab, and certolizumab pegol, and though highly effective in lowering inflammation, the efficacy must be weighed against the potential for adverse events. The treatment-induced immunosuppression is suspected to increase the risk of infections, including the risk of reactivation of latent tuberculosis, as the TNF-&#x003b1; cytokine plays an important role in the immune function. In this topic highlight a short overview of the infection risk associated with TNF-&#x003b1; inhibiter therapy is outlined with a focus on the overall risk of serious infections, mycobacterial infection and latent viral infections.

Deterministic Parsing Model of the Compound Biological Effectiveness (<i>CBE</i>) Factor for Intracellular ¹⁰Boron Distribution in Boron Neutron Capture Therapy

Purpose: In defining the biological effects of the 10B(n, α)7Li neutron capture reaction, we have previously developed a deterministic parsing model to determine the Compound Biological Effectiveness (CBE) factor in Borono-Phenyl-Alanine (BPA)-mediated Boron Neutron Capture Therapy (BNCT). In present paper, we demonstrate that the CBE factor is directly and unambiguously derivable by the new formula for any case of intracellular 10Boron (10B) distribution, which is founded on this model for tissues and tumor. Method: To determine the CBE factor, we derive the following new calculation formula founded on the deterministic parsing model with three constants, CBE0, F, n and the eigen value Nth/Nmax. where, Nth and Nmax are the threshold value of boron concentration of N and saturation boron density in tissues and tumor. In order to determine these constants and the eigen values, iterative calculation technique was employed for the CEB factor and Nmax data set previously reported. Results and Conclusion: From the iterative calculation results, it is clear that the calculated CBE factor values obtained are almost identical to the original CBE factors and there is a good correlation between the original CBE factors and Nth/Nmax, when CBE0, F and n are given as 0.5, 8 and 3, respectively. These constants provide a better understanding of different types of intracellular10B distribution.

Determination of the Compound Biological Effectiveness (CBE) Factors Based on the <i>ISHIYAMA-IMAHORI</i>Deterministic Parsing Model with the Dynamic PET Technique

Purpose: In defining the biological effects of the 10B(n, α)7Li neutron capture reaction, we have proposed a deterministic parsing model (ISHIYAMA-IMAHORI model) to determine the Compound Biological Effectiveness (CBE) factor in Borono-Phenyl-Alanine (BPA)-mediated Boron Neutron Capture Therapy (BNCT). In present paper, we demonstrate a specific method of how the application of the case of application to actual patient data, which is founded on this model for tissues and tumor. Method: To determine the CBE factor, we derived the following new calculation formula founded on the deterministic parsing model with three constants, CBE0, F, n and the eigen value Nth/Nmax.? (1), where, Nth and Nmax are the threshold value of boron concentration of N and saturation boron density and CBE0, F and n are given as 0.5, 8 and 3, respectively. In order to determine Nth and Nmax in the formula, sigmoid logistic function was employed for 10B concentration data, Db(t) obtained by dynamic PET technique. (2), where, A, a and t0 are constants. Results and Conclusion: From the application of sigmoid function to dynamic PET data, it is concluded that the Nth and Nmax for tissue and tumor are identified with the parameter constants in the sigmoid function in Equation (2) as: (3). And the calculated CBE factor values obtained from Equation (1), with Nth/Nmax.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.

Prognostic value and predictive model of tumor markers in stageⅠtoⅢgastric cancer patients

BACKGROUND Preoperative serum tumor markers have been widely used in the diagnosis and treatment of gastric cancer patients.However,few studies have evaluated the prognosis of gastric cancer patients by establishing statistical models with multiple serum tumor indicators.AIM To explore the prognostic value and predictive model of tumor markers in stage I and III gastric cancer patients.METHODS From October 2018 to April 2020,a total of 1236 patients with stage I to III gastric cancer after surgery were included in our study.The relationship between serum tumor markers and clinical and pathological data were analyzed.We established a statistical model to predict the prognosis of gastric cancer based on the results of COX regression analysis.Overall survival(OS)was also compared across different stages of gastric cancer.RESULTS The deadline for follow-up was May 31,2023.A total of 1236 patients were included in our study.Univariate analysis found that age,clinical stage,T and N stage,tumor location,differentiation,Borrmann type,size,and four serum tumor markers were prognostic factors of OS(P<0.05).It was shown that clinical stage,tumor size,alpha foetoprotein,carcinoembryonic antigen,CA125 and CA19-9(P<0.05)were independent prognostic factors for OS.According to the scoring results obtained from the statistical model,we found that patients with high scores had poorer survival time(P<0.05).Furthermore,in stage I patients,the 3-year OS for scores 0-3 ranged from 96.85%,95%,85%,and 80%.In stage II patients,the 3-year OS for scores 0-4 were 88.6%,76.5%,90.5%,65.5%and 60%.For stage III patients,3-year OS for scores 0-6 were 70.9%,68.3%,64.1%,50.9%,38.4%,18.5%and 5.2%.We also analyzed the mean survival of patients with different scores.For stage I patients,the mean OS was 55.980 months.In stage II,the mean OS was 51.550 months.The mean OS for stage III was 39.422 months.CONCLUSION Our statistical model can effectively predict the prognosis of gastric cancer patients.