PURPOSE: Despite plasma biomarkers offering a number of advantages over tissue-based markers, the relationship between serum vascular endothelial growth factor (VEGF) and VEGF receptor (VEGF-R) tumor expression in colorectal cancer (CRC) is still unclear. This study was designed to establish the relationship between the concentration of serum VEGF and tumor VEGF-R expression in patients with CRC. METHODS: A prospective study of consecutive patients undergoing elective colorectal surgery during 1 year. Preoperative VEGF was determined by enzyme-linked immunosorbent assay and VEGF-R3 by immunochemistry. RESULTS: The initial sample included 134 patients with CRC diagnosis. Results showed significant association of serum values of VEGF with VEGF-R3 expression (P < 0.001), even in the presence of confounders (sex, age, body mass index, tumor location, and surgical approach). The estimated effect size was high (η² = 0.35). CONCLUSION: Serum VEGF has a significant correlation with tumoral VEGF-R3 expression in CRC.
Biomarkers ; Body Mass Index ; Colorectal Neoplasms ; Colorectal Surgery ; Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunochemistry ; Immunohistochemistry ; Plasma ; Prospective Studies ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

OBJECTIVE: Human papillomavirus (HPV) 16 is the most carcinogenic HPV genotype. We investigated if HPV16 L1 capsid protein and E2/E6 ratio, evaluated by cervical cytology, may be used as biomarkers of ≥cervical intraepithelial neoplasia (CIN) 2 lesions. METHODS: Cervical specimens were obtained from 226 patients with HPV16 single infection. Using cytology specimen, L1 capsid protein and E2/E6 ratio were detected and the results were compared with those of the conventional histologic analysis of cervical tissues (CIN1–3 and squamous cell carcinoma [SCC]) to evaluate the association. RESULTS: The L1 positivity of CIN2/3 was significantly lower than that of normal cervical tissue (p < 0.001) and SCC demonstrated significantly lower L1 positivity than CIN1 (p < 0.001). The mean E2/E6 ratios of specimens graded as SCC (0.356) and CIN2/3 (0.483) were significantly lower than those of specimens graded as CIN1 (0.786) and normal (0.793) (p < 0.05). We observed that area under the receiver operating characteristic curve (AUC) for E2/E6 ratio (0.844; 95% confidence interval [CI]=0.793–0.895) was higher than that for L1 immunochemistry (0.636; 95% CI=0.562–0.711). A combination of E2/E6 ratio and L1 immunocytochemistry analyses showed the highest AUC (0.871; 95% CI=0.826–0.917) for the prediction of ≥CIN2 lesions. CONCLUSION: To our knowledge, this is the first study to validate HPV L1 capsid protein expression and decreased HPV E2/E6 ratio as valuable predictive markers of ≥CIN2 cervical lesions. Cervical cytology may be analyzed longitudinally on an outpatient basis with noninvasive procedures as against invasive conventional histologic analysis.
Area Under Curve ; Biomarkers* ; Capsid Proteins ; Carcinoma, Squamous Cell* ; Cervical Intraepithelial Neoplasia ; Epithelial Cells* ; Genotype ; Humans ; Immunochemistry ; Immunohistochemistry ; Outpatients ; ROC Curve ; Squamous Intraepithelial Lesions of the Cervix* ; Uterine Cervical Neoplasms ; Virus Integration

The retinal degeneration resulting from elevated intraocular pressure was evaluated through functional and morphological analyses, for better understanding of the pathophysiology of glaucoma. Ocular hypertension was induced via unilateral episcleral venous cauterization in rats. Experimental time was set at 1 and 3 days, and 1, 2, 4, and 8 weeks post-operation. Retinal function was analyzed using electroretinography. For morphological analysis, retinal tissues were processed for immunochemistry by using antibodies against the calcium-sensing receptor and calcium-binding proteins. Apoptosis was analyzed using the TUNEL method and electron microscopy. Amplitudes of a- and b-wave in scotopic and photopic responses were found to be reduced in all glaucomatous retinas. Photopic negative response for ganglion cell function significantly reduced from 1-day and more significantly reduced in 2-week glaucoma. Calcium-sensing receptor immunoreactivity in ganglion cells remarkably reduced at 8 weeks; conversely, protein amounts increased significantly. Calcium-binding proteins immunoreactivity in amacrine cells clearly reduced at 8 weeks, despite of uneven changes in protein amounts. Apoptosis appeared in both photoreceptors and ganglion cells in 8-week glaucomatous retina. Apoptotic feature of photoreceptors was typical, whereas that of ganglion cells was necrotic in nature. These findings suggest that elevated intraocular pressure affects the sensitivity of photoreceptors and retinal ganglion cells, and leads to apoptotic death. The calcium-sensing receptor may be a useful detector for alteration of extracellular calcium levels surrounding the ganglion cells.
Amacrine Cells ; Animals ; Antibodies ; Apoptosis ; Calcium ; Calcium-Binding Proteins ; Cautery ; Electroretinography ; Ganglion Cysts ; Glaucoma ; Immunochemistry ; In Situ Nick-End Labeling ; Intraocular Pressure ; Methods ; Microscopy, Electron ; Ocular Hypertension ; Rats ; Receptors, Calcium-Sensing ; Retina ; Retinal Degeneration ; Retinal Ganglion Cells ; Retinaldehyde

It is widely accepted that altered metabolism contributes to cancer growth and has been described as a hallmark of cancer. Our view and understanding of cancer metabolism has expanded at a rapid pace, however, there remains a need to study metabolic dependencies of human cancer in vivo. Recent studies have sought to utilize multi-modality imaging (MMI) techniques in order to build a more detailed and comprehensive understanding of cancer metabolism. MMI combines several in vivo techniques that can provide complementary information related to cancer metabolism. We describe several non-invasive imaging techniques that provide both anatomical and functional information related to tumor metabolism. These imaging modalities include: positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) that uses hyperpolarized probes and optical imaging utilizing bioluminescence and quantification of light emitted. We describe how these imaging modalities can be combined with mass spectrometry and quantitative immunochemistry to obtain more complete picture of cancer metabolism. In vivo studies of tumor metabolism are emerging in the field and represent an important component to our understanding of how metabolism shapes and defines cancer initiation, progression and response to treatment. In this review we describe in vivo based studies of cancer metabolism that have taken advantage of MMI in both pre-clinical and clinical studies. MMI promises to advance our understanding of cancer metabolism in both basic research and clinical settings with the ultimate goal of improving detection, diagnosis and treatment of cancer patients.
Diagnosis ; Humans ; Immunochemistry ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Metabolism ; Optical Imaging ; Positron-Emission Tomography

OBJECTIVE: To investigate the expression of claudin 4 (CLDN4) in cervical tissues from patients with different cervical lesions, and to explore the value of combined detection of CLDN4 and high risk human papilloma virus (HR-HPV). METHODS: The cervical tissue specimens of low-grade squamous intraepithelial lesion (LSIL, =30), high-grade squamous intraepithelial lesion (HSIL, =30), squamous cell carcinoma (SCC, =30) as well as chronic cervicitis (control, =30) were collected from the Sir Run Run Shaw Hospital of Zhejiang University during June 2015 and December 2016. The expression of CLDN4 protein in tissue specimens was detected by immunohistochemistry, HR-HPV was detected by real-time quantitative PCR, and the cervical exfoliated cells were examined by thinprep cytologic test (TCT). The ROC curve was applied to analyze the diagnostic value of TCT combined with HR-HPV and CLDN4 combined with HR-HPV tests for HSIL and SCC of the cervix. RESULTS: With the increase of the severity of cervical lesions, the positive rate of CLDN4 expression rose (=0.832, <0.05). Positivity of both HR-HPV infection and CLDN4 expression was found mainly in the HSIL and SCC groups. The areas under curve (AUC) of TCT combined with HR-HPV and CLDN4 combined with HR-HPV tests for diagnosis of HSIL and SCC were 0.683 and 0.633, respectively; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of TCT combined with HR-HPV test for diagnosis of HSIL and SCC were 100.0%, 36.7%, 61.2%, 100.0% and 46.7% respectively; those of CLDN4 combined with HR-HPV test were 96.7%, 30.0%, 58.0%, 90.0% and 55.0%, respectively. CONCLUSIONS CLDN4 expression may be related to the occurrence and development of cervical carcinoma and precancerous lesions. CLDN4 combined with HR-HPV test may be used for diagnosis of HSIL and SCC of the cervix clinically.
Carcinoma, Squamous Cell ; diagnosis ; virology ; Cervical Intraepithelial Neoplasia ; diagnosis ; virology ; Claudin-4 ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunochemistry ; Papillomaviridae ; isolation & purification ; Real-Time Polymerase Chain Reaction ; Squamous Intraepithelial Lesions of the Cervix ; virology ; Uterine Cervical Neoplasms ; diagnosis

In the developed and developing world, opioid consumption in combination with alcohol has become one of the substances abused. In this experiment, we examined the effects of alcohol, morphine, and morphine+alcohol combination on cognitive functions and neuroinflammatory responses in the medial prefrontal cortex (mPFC) of juvenile male rats. Alcohol (1.0 ml of 15% v/v ethanol twice daily, subcutaneously, 7 hours apart), morphine (0.5 ml/kg of 0.4 mg/kg morphine chlorate twice daily, subcutaneously, 7 hours apart), morphine+alcohol co-treatment (0.5 ml/kg of 0.4 mg/kg morphine chlorate+1.0 ml of 15% v/v ethanol twice daily, subcutaneously, 7 hours apart) were administered for 21 days. Treatment with morphine+alcohol significantly impairs cognition functions in the Morris water maze, passive avoidance, and novel object recognition tests, furthermore, the treatment significantly increased the quantitative count of astrocytic cells and also conferred marked neuronal cell death in the mPFC, which were studied by glial fibrillary acidic protein immunochemistry for astrocytes and Cresyl violet for Nissl's substance distribution in neurons respectively. These results suggest that alcohol, morphine, and morphine+alcohol co-treatment may trigger cognitive deficits and neuroinflammatory responses in the brain.
Alcohols ; Animals ; Astrocytes ; Brain ; Cell Death ; Cognition Disorders ; Cognition* ; Ethanol ; Glial Fibrillary Acidic Protein ; Humans ; Immunochemistry ; Male* ; Morphine ; Neurons ; Prefrontal Cortex* ; Rats* ; Viola ; Water

Objective: To analyze the effect of colorectal cancer screening in the general population in Guangzhou, and provide evidence for the for development of colorectal cancer screening policy and strategy. Methods: The data of colorectal cancer screening in Guangzhou during 2015- 2016 were collected. The participation, the positive rate of fecal occult blood test, the detection rate of colonoscopy and screening effect of colonoscopy were evaluated. Results: A total of 220 834 residents aged 50-74 years received the screening, and the positive rate of the screening was 16.77% (37 040 cases). Colonoscopy was performed for 7 821 cases (21.12%). Colorectal lesions were found in 4 126 cases (52.76%), of which 614 (7.85%) and 73 (0.93%) and 230 (2.94%) were identified as advanced adenoma, severe dysplasia lesions and colorectal cancers, respectively. The detection rates of all colorectal lesions were higher in men than in women (all P<0.01). The diagnostic rate of early lesion was 87.24%, and 99 early cancer cases were found, accounting for 46.26% of the total cases. The overall screening detection rate of colorectal cancer was 104.15/100 000, higher than the incidence rate (81.18/100 000) in colorectal cancer surveillance (P<0.001), but age group <70 years had higher detection rate, age group ≥70 years had higher incidence rate. Conclusions: The colorectal cancer screening strategy in Guangzhou is effective in the detection of the population at high risk, increase the detection rate of colorectal lesions, early diagnosis rate of precancerous lesions and diagnosis rate of early colorectal cancer. The benefit in those aged ≤69 years was more obvious than that in those aged 70-74 years. It is necessary to improve the compliancy of colorectal cancer screening in population at high risk.
Adenoma/prevention & control* ; Aged ; China/epidemiology* ; Colonoscopy/statistics & numerical data* ; Colorectal Neoplasms/prevention & control* ; Early Detection of Cancer/methods* ; Female ; Humans ; Immunochemistry ; Male ; Mass Screening/statistics & numerical data* ; Middle Aged ; Occult Blood ; Predictive Value of Tests

Notalgia paresthetica (NP) is a chronic localized itch, affecting mainly the inter-scapular area particularly between the T2-T6 dermatomes. Occasionally it has a more widespread distribution and involves the shoulders, back, and upper chest. There are no specific cutaneous signs, apart from those attributed to scratching and rubbing. Various etiologies have been reported, but the cause of NP is not established. The current hypothesis regarding its etiology postulates that a neuropathic itch develops due to nerve entrapment of the posterior rami of spinal nerve arising at T2-T6. Another recent documented case showed an increase in the number of intradermal nerves by neural immunochistochemistry staining of S-100 protein, protein gene product 9.5 (PGP 9.5). Herein, we experienced an uncommon case of NP of the back and tried to clarify pathogenesis by using quantitative sensory testing, such as neurometer and Von-Frey filaments. Also, we performed neural immunochemistry to confirm an increase in nerve fibers at the site of the lesion.
Immunochemistry ; Nerve Compression Syndromes ; Nerve Fibers ; Pregabalin* ; S100 Proteins ; Shoulder ; Spinal Nerves ; Thorax

The Wnt signaling pathway and its key component β-catenin have critical roles in the development of diseases such as tumors in mammals. However, little has been reported about involvement of the Wnt/β-catenin signaling pathway in canine mammary tumors (CMTs). The present study detected expression of 30 Wnt signaling pathway-related genes in CMTs; the results are potentially useful for molecular-based diagnosis of CMTs and the development of new targeted therapies. Significant upregulations of dickkopf-1 protein, secreted frizzled-related sequence protein 1 (SFRP1), frizzled 3, β-catenin, and lymphoid enhancer-binding factor 1 (LEF1) were detected in highly malignant CMTs compared to levels in normal mammary gland tissues; moreover, highly significant upregulation of WNT5A was observed in low malignancy CMTs. Downregulation was only detected for SFRP4 in malignant CMT samples. The subcellular location of β-catenin and cyclin D1 in 100 CMT samples was investigated via immunohistochemical analysis, and significantly increased expressions of β-catenin in cytoplasm and cyclin D1 in nuclei were revealed. Western blotting analysis revealed that the expression of β-catenin and LEF1 increased in in the majority of CMT samples. Taken together, the results provide important evidence of the activation status of the Wnt pathway in CMTs and valuable clues to identifying biomarkers for molecular-based diagnosis of CMT.
beta Catenin ; Biomarkers ; Blotting, Western ; Cyclin D1 ; Cytoplasm ; Diagnosis ; Down-Regulation ; Immunochemistry* ; Lymphoid Enhancer-Binding Factor 1 ; Mammals ; Mammary Glands, Human ; Polymerase Chain Reaction* ; Up-Regulation ; Wnt Signaling Pathway

Solitary Fibrous tumor is usually arising in the pleura of the thoracic cavity and it has been described in a variety of extrapleural sites including the abdominal cavity, soft tissue, upper respiratory tract and rarely in head and neck region. We experienced a rare case of solitary fibrous tumor in the parotid gland. A 49-year-old woman presented with a painless mass in the left parotid. The mass was well-demarcated and easily dissected, and it showed a patternless arrangement of potential malignant spindle cells in a fibrotic background and prominent vascular structures. In immunochemistry, the mass cells were positive for CD34, vimentin, and negative for actin, S-100 protein, and cytokeratins. Therefore, the parotid mass diagnosed as SFT. During the 24 months of follow-up, there was no recurrence of tumor growth.
Abdominal Cavity ; Actins ; Female ; Follow-Up Studies ; Head ; Humans ; Immunochemistry ; Keratins ; Middle Aged ; Neck ; Parotid Gland* ; Pleura ; Recurrence ; Respiratory System ; S100 Proteins ; Salivary Glands ; Solitary Fibrous Tumors* ; Thoracic Cavity ; Vimentin