Cancer is still one of the major diseases threatening human life and health. At present, how to achieve precise diagnosis and treatment of tumors is the biggest challenge in cancer treatment. Prodrugs use the tumor specificity of targeting molecules to deliver anticancer drugs to tumor sites, which can effectively improve drug bioavailability, therapeutic efficacy and safety, and are currently a hot spot in the research and development of anticancer drugs. The targeting molecules of prodrugs mainly include nucleic acid aptamers, polymers, antibodies, polypeptides, etc. Among them, polypeptides have the advantages of good biocompatibility, controllable degradation performance, high in vivo responsiveness, and simple and easy preparation methods, and are widely used. It is used to construct peptide-drug conjugates (PDC) prodrugs to achieve targeted therapy of tumors. In recent years, with the development of phage peptide library technology and peptide standard solid-phase synthesis technology, more and more targeted peptides have been discovered and effectively synthesized and modified, providing strong support for the development of PDC. This review briefly introduces the types and functions of functional peptides and linkers in PDC, and discusses the application of PDC in chemotherapy, immunotherapy and photodynamic therapy in tumor targeted diagnosis and treatment, and finally summarizes the difficulties faced by PDC drug development.

Chromosomes, Human, Pair 14 ; Humans ; Ring Chromosomes ; Syndrome

Objective: To investigate the benzo[a]pyrene ( B[a]P ) diolepoxide ( BPDE )-DNA adduct levels in offspring rats with intrauterine exposure to B[a]P, and examine the effects of BPDE-DNA adduct levels on pancreatic functional impairment and glucose metabolism in offspring rats. Methods: Forty pregnant rats were randomly divided into the blank control group, standard-dose group, low-dose group, medium-dose group and high-dose group (daily dose of 0, 2, 200, 800, 1 600 μg/kg B[a]P, respectively), of 8 animals in each group. Rats in the B[a]P treatment groups were administered by oral gavage with a mixture of B[a]P and corn oil at a dose of 0.2 mL/100 g body weight since day 1 of pregnancy until 21 days after delivery, while rats in the blank control group were given the same volume of coin oil by oral gavage. The BPDE-DNA adduct levels were measured and the pancreatic development was observed in the offspring rats 2 and 21 days and 12 weeks after birth, and the correlation between pancreas volume index and dose of exposure to B[a]P was examined using Spearman's rank correlation analysis. In addition, glucose metabolism was measured in offspring rats 12 months after birth using glucose tolerance test ( GTT ) and insulin tolerance test ( ITT ). Results: There was no abnormal appearance, death, abortion or preterm birth in pregnant or offspring rats in the five groups, and no significant differences were seen in activity, diet, drinking water or mental status in rats. The greatest level of BPDE-DNA adducts was measured in offspring rats 2 days after birth, with median levels ( interquartile range ) of 1 089.60 ( 586.10 ) to 1 405.49 ( 346.47 ) pg/mL, and no BPDE-DNA adducts were found in offspring rats 12 weeks after birth. The pancreas volume index correlated negatively with the dose of exposure to B[a]P in offspring rats 2 ( rs=-0.620, P=0.001 ) and 21 days after birth ( rs=-0.801, P=0.001 ). Hypoplasia of pancreas with loose tissues was seen in offspring rats 2 days after birth, while well pancreatic development was found in offspring rats 12 weeks after birth, with tight exocrine portion. GTT showed an increase in glucose levels in offspring rats in all five groups following abdominal injection of glucose and declined 30 min post-injection ( F=365.578, P<0.001 ), and ITT showed a tendency towards a decline in glucose levels in offspring rats in all five groups ( F=461.215, P<0.001 ). Conclusions The levels of BPDE-DNA adducts in offspring rats increase with the dose of intrauterine B[a]P exposure, and insulin resistance and impaired glucose tolerance occur 12 months post-exposure to B[a]P. Intrauterine B[a]P exposure affects pancreatic development in offspring rats and causes abnormal glucose metabolism in adult offspring rats.

Objective To compare the sonographic and pathologic features of calcified and non-calcified ductal carcinoma in situ DCIS Methods A total of 83 lesions in 82 consecutive patients with pathologically confirmed pure DCIS were recruited One patient had bilateral lesions All lesions were divided into calcified DCIS and non-calcified DCIS according to the presence of calcifications on mammography Their sonographic features and pathologic reports for all patients with DCIS were retrospectively reviewed Statistical comparisons were performed using the chi-square test Results 1 Calcified DCIS showed positive ultrasound US findings in 80% 44 55 of cases The most common US finding was nonmass lesions 43 6% 24 55 Nine cases had pure ductal dilatations 16 4% 9 55 Non-calcified DCIS showed positive US findings in 96 4% 27 28 of cases The most common US finding was mass 89 2% 25 28 Two cases had pure ductal dilatations 7 1 % 2 28 No significant difference was found in the shape margin orientation posterior feature of a mass between the calcified and non-calcified groups P >0 05 Significant difference was observed in the size boundary echogenicity on ultrasound of the two groups P <0 05 2 At histopathology the pathological scores high nuclear grade positive ER status positive PR status positive Ki67 status and the presence of Her-2 neu oncogene were more common in the calcified group than in the non-calcified group Conclusions Calcified and non-calcified pure DCIS have different pathologic and sonographic features Calcified DCIS has more aggressive histological features than non-calcified DCIS.

Objective: To observe the effects of perinatal exposure to benzo[a]pyrene (B[a]P) on the expression of pancreatic duodenal homeobox-1 (PDX-1) and mitochondrial transcription factor A (TFAM) and mitochondrial DNA copy number in offspring mice, and to explore the role of maternal exposure to B[a]P in the pancreatic function damage of offspring mice. Methods: Forty pregnant rats were randomly divided into the control group, the lowest dose group (2 μg/kg), the low dose group (200 μg/kg), medium dose group (800 μg/kg) and high dose group (1 600 μg/kg), with 8 rats in each group. From day 1 of pregnancy, each exposed group was given 0.2 mL/100 g body weight of B[a]P and corn oil mixture by gavage once a day until 3 weeks after delivery, while the control group was given the same dose of corn oil. The pancreatic tissue of three-week-old mice were collected after abdominal anesthesia for insulin immunohistochemical detection. The protein and mRNA expression levels of PDX-1 and TFAM, as well as mitochondrial DNA copy number were detected. Spearman rank correlation analysis was used to analyze the correlation between B[a]P exposure dose and the above indicators. Results: The insulin-positive area ratio and average optical density of insulin in the medium and the high dose groups were significantly lower than those in the control group (all P<0.05). The insulin-positive area ratio and average optical density of insulin were negatively correlated with the B[a]P dose (rs=-0.862 and -0.858, both P<0.05). The protein expression levels of PDX-1 and TFAM in the high dose group were significantly lower than those in the control group (both P<0.05). The protein expression levels of PDX-1 and TFAM were negatively correlated with the B[a]P dose (rs=-0.756 and -0.799, both P<0.05). The mRNA expression levels of PDX-1 and mitochondrial DNA copy number in the medium and high dose groups were significantly lower than those in the control group, and the mRNA expression level of TFAM in the high dose group was significantly lower than that in the control group (all P<0.05). The mRNA expression levels of PDX-1, TFAM, and mitochondrial DNA copy number were negatively correlated with the B[a]P dose (rs=-0.722, -0.550 and -0.840, all P<0.05). Conclusion Perinatal exposure to B[a]P can induce the damage of islet β cells in offspring rats, which may be related to the decreased expression of PDX-1 and TFAM and the copy number of mitochondrial DNA.

Adolescent ; Child ; Child, Preschool ; Cytomegalovirus Infections ; complications ; Female ; Humans ; Kidney Diseases ; etiology ; Kidney Glomerulus ; pathology ; Male

Objective To assess the diagnostic value of ~(18)F-FDG PET/CT combining chest breath-hold spiral CT in preoperative primary tumor staging (T stage) of non-small lung cell cancer (NSCLC) before operation. Methods Ninety NSCLC patients underwent curative surgical resection after integrated ~(18)F-FDG PET/CT and chest breath-hold spiral CT examination. Two experienced radiologists blindedly staged all primary tumors in consensus by CT and PET/CT images. Surgical and histopathologic results served as the golden standard for determing the staging value of CT and PET/CT. T stage was assigned according to the seventh edition of TNM Classification of Malignant Tumors adopted by American Joint Committee on Cancer. Results According to pathological results, CT and PET/CT classified T stage accurately in 75.56% and 82.22%, respectively (P=0.03). CT and PET/CT accurately classified 3 and 6 patients respectively in 8 patients of central cancer with atelectasis, 2 and 4 metastases respectively in 5 patients at the ipsilateral lung. Conclusions Being able to describe the morphology, size and invasive region of primary tumor in NSCLC distinctly, CT is the main imaging method for T stage. ~(18)F-FDG PET/CT has unique value in differentiating center cancer with atelectasis and diagnosing pulmonary metastasis.

Objective To assess the diagnostic value of ~(18)F-FDG PET/CT combined with breath-hold spiral CT in pulmonary nodules. Methods One hundred and fifty-four patients with 171 pulmonary nodules (≤3 cm) were studied. Each patient underwent ~(18)F-FDG PET/CT (16 slices) examination during mild respiration and breath-hold spiral CT scan, while 123 patients underwent dual-time-point PET/CT examination. The diagnostic efficacy of ~(18)F-FDG PET/CT combined with breath-hold spiral CT,~(18)F-FDG PET/CT, breath-hold spiral CT and taking SUV_(max)≥2.50 as the threshold value for malignancy were compared. All results were proved by pathologically, or by diagnostic therapy or by clinical follow-up. Results The SUV_(max routine) was 4.51±3.06 in 118 malignant nodules, and 2.07±1.30 in 53 benign nodules. The sensitivity, specificity, accuracy and Youdenindex of ~(18)F-FDG PET/CT combined with breath-hold spiral CT was 95.80%, 81.10%, 91.20%and 0.77, respectively, higher than those of other three methods. Conclusion ~(18)F-FDG PET/CT combined with breath-hold spiral CT has high diagnostic value in the differentiation of pulmonary nodules.

Objective To assess the value of ~(18)F-FDG PET/CT in detecting primary tumors of patients with bone metastases, and to observe PET/CT characteristics of different types of bone metastases. Methods Whole-body ~(18)F-FDG PET/CT images of 34 patients with metastatic bone from unknown primary tumor (CUP) were retrospectively analyzed, and SUVmax was compared in osteolytic and osteoblastic subgroups based on CT characteristics. Results Diagnosis of these patients were confirmed by histopathological findings or ≥3 months follow-up. Primary tumors were detected with PET/CT in 22 patients (64.71%). SUV_(max) was 6.78±3.66 in 23 osteolytic metastases, and 4.13±1.69 in 11 osteoblastic metastases (P＜0.05). Conclusion ~(18)F-FDG PET/CT is helpful to find the localization of unknown primary tumors in patients with bone metastases, and to make treatment Planning. Osteolytic metastases show higher metabolic activity on ~(18)F-FDG PET/CT.

The purpose of this study is to investigate the enantioselectivity of norgestrel (NG) transdermal permeation and the potential influence of linalool and lipids on the enantioselectivity. In vitro skin permeation studies of NG across the excised rat skins were performed with Valia-Chien diffusion cells, and the permeation samples were analyzed by enantioselective HPLC. The possible enantioselective permeation of NG across intact rat back skin and lipids extracted rat back skin and the influence of linalool were evaluated. The skin permeation rate of dl-NG was two times higher than that of l-NG when donor solutions (EtOH/H2O 2 : 8, v/v) containing l-NG or dl-NG. It may be mainly attributed to the solubility discrepancy between enantiomer and racemate. The enantioselective permeation of dl-NG across intact rat skin was observed when the donor solutions containing dl-linalool. The permeation flux of l-NG was 22% higher than that of d-NG. But interestingly, the enantioselective permeation of dl-NG disappeared under the same experimental condition except that the lipid extracted rat skin was used. Attenuated total reflection-fourier transform infrared spectroscopy analysis of stratum corneum showed that the wave number for asymmetric CH2 stretching vibrations of lipids treated with dl-linalool was greater than that of the control. The results indicated that the enantioselective permeation of NG may be contributed by the interaction between dl-linalool and lipids. More than half of lipids were composed of ceramides. The stereospecific interaction maybe existed among chiral enhancer (linalool), lipids (ceramides) and/or chiral drugs (NG).
Administration, Cutaneous ; Animals ; Lipids ; pharmacology ; Monoterpenes ; pharmacology ; Norgestrel ; pharmacokinetics ; Rats ; Skin Absorption ; drug effects ; Spectroscopy, Fourier Transform Infrared ; Stereoisomerism