Cancer Testis Antigens: Novel Biomarkers and Targetable Proteins for Ovarian Cancer

Ovarian cancer is the fifth leading cause of cancer death in women and the leading cause from gynecological malignancies. Despite the recently improved outcomes of new chemotherapeutical agents in the therapy of ovarian cancer and the increased 5-year survival rate, the mortality of this malignancy disease remains unchanged. Ovarian cancer therapy is often correlated to the stage of the tumor, but the first step is usually surgical treatment. Afterward, various courses of chemotherapy and radiation are suggested. Obviously, the higher the developmental stage of the tumor, the less the probability is in eradicating it surgically, especially in relation to metastasis. It is clear that an early diagnosis of ovarian cancer is important for the survival of these patients. In order to identify ovarian cancer patients in the early stages, a number of studies are focusing on a particular class of antigens called cancer testis antigens. These antigens display high expression in tumors of different histology, but are normally restricted to the testis and have low or no expression in normal tissues. The testes are an immunologically-privileged site due to the presence of tight junctions between adjacent Sertoli cells that constitute the blood-testis barrier, which prevents auto-immune reactions. In the past few years, some of these antigens were demonstrated to be very promising for the early diagnosis and development of vaccines for ovarian cancer. This review aims to underline the most reliable cancer testis antigens under investigation at this moment.     

Cancer Testes Antigens in Breast Cancer: Biological Role,Regulation, and Therapeutic Applicability

Breast cancer remains one of the leading causes of death among women across the world. The last few decades have seen significant reduction in mortality owing to earlier detection and better adjuvant treatments that were developed based on clinical staging and morphological features. As these treatments have evolved, the heterogeneity of breast cancer poses a new challenge, since there is no standard gold-therapy suitable for all tumors of the mammary gland. Therefore, contemporary management and research efforts are directed toward specific prognostic and predictive molecular signatures that can guide targeted individualized therapy. The goal of ongoing research in this field is to identify specific molecular targets for developing novel therapeutic approaches. These targets can also serve to improve screening of breast cancer. This review focuses on the role of cancer testis antigens (CTAs) in breast carcinogenesis and explores the potential for development of targeted screening and therapeutic approaches. Normally found in the testes, these antigens are highly correlative with cancers of the breast, skin, and ovaries. These implications have been further corroborated through uncovering the interaction of CTAs with genes and proteins involved in tumor suppression and homeostasis like p53. There is some evidence that these genes can be targeted for early detection in addition to being candidates for cancer immunotherapy.     

淫羊藿苷调节雄性大鼠生殖功能

目的:探讨淫羊藿苷在环磷酰胺诱导的大鼠睾丸生精障碍动物模型中的作用,研究淫羊霍苷对睾丸功能的影响.方法:分为空白对照组、阴性对照组、模型组、淫羊藿苷治疗组;H-E染色观察睾丸组织结构变化,TUNEL方法检测睾丸生殖细胞凋亡,放射免疫法检测血清睾酮.结果:睾丸H-E染色切片观察显示模型组睾丸生精小管直径缩小,间距增宽,生精上皮变薄,生殖细胞数量减少,生精小管多未见精子形成,与空白对照组比较其生精小管结构变化显著;淫羊藿苷治疗组与模型组比较生精小管壁增厚,含有精子的生精小管明显增多.睾丸生精小管中生殖细胞凋亡的观察模型组与空白对照组比较其生殖细胞凋亡增多,变化显著;淫羊藿苷治疗组与模型组比较生精小管中生殖细胞凋亡数量明显减少.模型组与空白对照组比较血清睾酮明显降低;淫羊藿苷治疗组与模型组比较其血清睾酮明显增加.结论:淫羊藿苷对环磷酰胺诱导生精障碍的睾丸具有改善睾丸生精小管结构、减少生殖细胞凋亡、促进精子发生和间质细胞分泌睾酮的功能.     

Spontaneous regression of cystic dysplasia of the rete testis in an 18-month-old boy: the key role of ultrasonography

Cystic dysplasia of the rete testis (CDT) is a rare cause of scrotal swelling in children. It is a congenital disorder and it can be associated with other genitourinary abnormalities. At present, there is no clear consensus on treatment. Surgical approach has traditionally been the treatment of choice, while, more recently, conservative approach has been applied, justified by the benign nature of the lesion and after few cases of spontaneous regression have been documented. Ultrasonography, supported by negative tumor markers, plays a key role in the diagnostic work up and during observational follow-up. We report a further case of spontaneous regression of suspected CDT in an 18-month-old boy, who has been followed with clinic and ultrasonographic checks.     

Hesperidin protects testicular and spermatological damages induced by cisplatin in rats

The clinic usage of cisplatin, an anticancer drug, is limited due to it has many side effects in many systems and organs. In this context, it was aimed to investigate the protective effect of hesperidin, a citrus flavonoid, on testicular and spermatological damages induced by cisplatin in rats. The rats were randomly divided into four groups. The first group was kept as a control. In the second groups, cisplatin was given at the single dose of 7 mg kg^?1 intraperitoneally. In the third group, hesperidin was orally administered at the dose of 50 mg/kg day^?1 for 14 days. In the fourth group, cisplatin and hesperidin were given together at the same doses. Cisplatin treatment caused significant reductions enzymatic (SOD, CAT and GPx) and nonenzymatic (GSH) antioxidants and significant induction level of TBARS. In addition, cisplatin treatment caused decreased sperm motility, epididymal sperm concentration, increased abnormal sperm rate and histopathological damage. In contrast, hesperidin treatment significantly attenuated the harmful effects. In conclusion, this study clearly demonstrated that hesperidin has protective effects on cisplatin‐induced reproductive system toxicity depending on its antioxidant properties. Thus, it is thought that hesperidin may be useful against cisplatin toxicity in patients with cancer in terms of reproductive system.     

Mucocele of the appendix： An unusual cause of lower abdominal pain in a patient with ulcerative colitis-. A case report and review of literature

The authors report the case of a 60-year-old male patient. In November 2001 he developed intestinal symptoms of bloody diarrhea and abdominal pain. Colononoscopy and biopsy established the diagnosis of ulcerative colitis (proctosigmoiditis). The disease activity was moderate at the beginning. No significant laboratory alterations were found (including CEA, CA19-9), and mesalazine was started orally. He was in remission until November 2003, when he was admitted to our Outpatient Clinic for upper and right lower abdominal pain and bloody diarrhea. Colonoscopy found proctosigmoiditis with a moderate activity, gastroscopy revealed chronic gastritis, laboratory data was normal. Treatment was amended with mesalazine clysma and methylprednisolone (16 mg) orally. Symptoms ameliorated; however, right lower abdominal pain persisted. US and CT examinat'on demonstrated a pericecal cystic mass (11 cm×3.5 cm). At first pericecal abscess was suspected, as the previous US examination (6 mo earlier) had revealed normal findings. Fine needie aspiration was performed. Cytology confirmed the diagnosis of mucocele. The patientunderwent partial cecum resection and extirpation of the mucocele. He recovered well and the final histology revealed a cystadenoma of the appendix. Follow up was started. The pati雗t is now free of symptoms. Although primary adenocarcinoma of the appendix is uncommon, the authors emphasize that preoperative diagnosis of an underlying malignancy in a mucocele is important for pati雗t management; however, it is difficult on imaging studies.     

Genetic variants of immunoglobulin γ and κ chains influence humoral immunity to the cancer‐testis antigen XAGE‐1b (GAGED2a) in patients with non‐small cell lung cancer

GM (γ marker) allotypes, genetic variants of immunoglobulin γ chains, have been reported to be associated strongly with susceptibility to lung cancer, but the mechanism(s) underlying this association is not known. One mechanism could involve their contribution to humoral immunity to lung tumour‐associated antigens. In this study, we aimed to determine whether particular GM and KM (κ marker) allotypes were associated with antibody responsiveness to XAGE‐1b, a highly immunogenic lung tumour‐associated cancer‐testis antigen. Sera from 89 patients with non‐small cell lung cancer (NSCLC) were allotyped for eight GM and two KM determinants and characterized for antibodies to a synthetic XAGE‐1b protein. The distribution of various GM phenotypes was significantly different between XAGE‐1b antibody‐positive and ‐negative patients (P = 0·023), as well as in the subgroup of XAGE‐1b antigen‐positive advanced NSCLC (P = 0·007). None of the patients with the GM 1,17 21 phenotype was positive for the XAGE‐1b antibody. In patients with antigen‐positive advanced disease, the prevalence of GM 1,2,17 21 was significantly higher in the antibody‐positive group than in those who lacked the XAGE‐1b antibody (P = 0·026). This phenotype also interacted with a particular KM phenotype: subjects with GM 1,2,17 21 and KM 3,3 phenotypes were almost four times (odds ratio = 3·8) as likely to be positive for the XAGE‐1b antibody as the subjects who lacked these phenotypes. This is the first report presenting evidence for the involvement of immunoglobulin allotypes in immunity to a cancer‐testis antigen, which has important implications for XAGE‐1b‐based immunotherapeutic interventions in lung adenocarcinoma.     

Effect of gestational exposure to perfluorononanoic acid on neonatal mice testes

Perfluoroalkyl acids (PFAAs) are widely used in commercial products and are found in many goods of daily use. Perfluorononanoic acid (PFNA) is one of the PFAAs that possesses endocrine disrupting properties and we have recently shown that PFNA affects testicular functions in Parkes mice. Exposure to environmental endocrine disruptors during fetal life is believed to affect gonadal development and they might produce reproductive abnormalities in males. Therefore, the present study examined the effect of gestational exposure to PFNA on the testes of neonatal mice offspring. Pregnant Parkes mice were orally administered PFNA (2 and 5 mg/kg body weight) or distilled water from gestational day 12 until parturition. Male pups were killed on postnatal day 3. PFNA treatment decreased testosterone biosynthesis by inhibiting expression of steroidogenic acute regulatory protein, cytochrome P450scc, and 3β‐ and 17β‐hydroxysteroid dehydrogenase; proliferation of testicular cells was also affected in treated mice. Furthermore, a marked decrease in expression of Wilms tumor 1, steroidogenic factor 1 and insulin‐like factor 3 was noted in neonatal mice testes, indicating that the PFNA treatment may affect the development of the testis. Moreover, observation of the dose‐related expression of anti‐müllerian hormone and c‐Kit in neonatal mice testes is also suggestive of an interference with gonadal development by PFNA exposure. In conclusion, the results suggest that the gestational exposure to PFNA decreased testosterone biosynthesis and altered the expression of critical factors involved in the development of the testis, thereby advocating a potential risk of PFNA to male reproductive health.