Establishment of an antibody specific for cancer-associated haptoglobin: a possible implication of clinical investigation

We previously found that the serum level of fucosylated haptoglobin (Fuc-Hpt) was significantly increased in pancreatic cancer patients. To delineate the mechanism underlying this increase and develop a simple detection method, we set out to generate a monoclonal antibody (mAb) specific for Fuc-Hpt. After multiple screenings by enzyme-linked immunosorbent assay (ELISA), a 10-7G mAb was identified as being highly specific for Fuc-Hpt generated in a cell line as well as for Hpt derived from a pancreatic cancer patient. As a result from affinity chromatography with 10-7G mAb, followed by lectin blot and mass spectrometry analyses, it was found that 10-7G mAb predominantly recognized both Fuc-Hpt and prohaptoglobin (proHpt), which was also fucosylated. In immunohistochemical analyses, hepatocytes surrounding metastasized cancer cells were stained by the 10-7G mAb, but neither the original cancer cells themselves nor normal hepatocytes exhibited positive staining, suggesting that metastasized cancer cells promote Fuc-Hpt production in adjacent hepatocytes. Serum level of Fuc-Hpt determined with newly developed ELISA system using the 10-7G mAb, was increased in patients of pancreatic and colorectal cancer. Interestingly, dramatic increases in Fuc-Hpt levels were observed at the stage IV of colorectal cancer. These results indicate that the 10-7G mAb developed is a promising antibody which recognizes Fuc-Hpt and could be a useful diagnostic tool for detecting liver metastasis of cancer.This study was performed as a research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct), Ministry of Education, Culture, Sports, Science and Technology of Japan and was supported by JSPS KAKENHI Grant Number JP16H05226

A poor prognostic metastatic nongestational choriocarcinoma of the ovary: a case report and the literature review

Abstract Background Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought to be worse than that of the gestational type in patients with metastatic disease. We present a case of metastatic pure ovarian choriocarcinoma with poor prognosis in which the origin was identified as nongestational by DNA short tandem repeat (STR) analysis. Case presentation A nulliparous woman in her thirties with metastatic choriocarcinoma was referred to our hospital after initial treatment proved unsuccessful. Two months earlier, she had undergone brain tumor resection and histological examination confirmed choriocarcinoma. Serum human chorionic gonadotropin (hCG) concentration at initial diagnosis was 5030 IU/L. Two cycles of a combination chemotherapy regimen of methotrexate, etoposide, and actinomycin-D (MEA therapy), which is commonly used for gestational choriocarcinoma, was administered. However, the disease could not be controlled. Imaging modalities at presentation revealed tumor present in the left ovary and left lung, but not in the uterus, which led us think that the choriocarcinoma was nongestational. Bleomycin, etoposide, and cisplatin (BEP therapy) which is commonly used for nongestational choriocarcinoma (malignant germ cell tumor) and surgical resection of the uterus, bilateral ovaries, and an affected part of the left lung led to the nadir level of hCG, but the tumor relapsed and levels of hCG again increased. To investigate the origin of choriocarcinoma, we performed DNA STR analysis of tumor cells and oral mucosal cells. Analysis revealed the origin of the choriocarcinoma as nongestational, as the genotype of tumor cells entirely corresponded with that of oral mucosal cells. BEP therapy and chemotherapy regimens administered for nongestational choriocarcinoma and gestational choriocarcinoma proved ineffective, and the patient died 21 months after diagnosis of metastatic choriocarcinoma. Conclusion Metastaic nongestational pure choriocarcinoma of ovary is an extremely rare and an aggressive disease, frequently resulting in poor outcome

A case of complete remission of intractable gestational choriocarcinoma with subsequent chemotherapy after pembrolizumab

Objective: Gestational choriocarcinoma is a gestational trophoblastic neoplasia (GTN) that originates from abnormal trophoblast proliferation. Although chemotherapy is effective for choriocarcinoma, personalized treatment becomes essential when patients develop chemoresistance. Here, we present the clinical course of a case of intractable choriocarcinoma that achieved complete remission with pembrolizumab following cytotoxic chemotherapy. Case report: A 38-year-old woman was initially diagnosed with low-risk GTN and treated with single- and multi-agent chemotherapy. She underwent a hysterectomy and was diagnosed with pathological choriocarcinoma with high-risk GTN. She was treated with multiple courses of several chemotherapy regimens. However, she did not achieve remission. Her choriocarcinoma showed high microsatellite instability; therefore, she took ten courses of pembrolizumab, but her hCG value increased. Subsequently, she underwent eight courses of paclitaxel and carboplatin alternating with paclitaxel and etoposide and achieved remission. Conclusion: This case suggests that pembrolizumab may improve the efficacy of subsequent chemotherapy

Unmet need for contraception among married women in the Kyrgyz Republic using the datasets from the 2006, 2014 and 2018 Multiple Indicator Cluster Survey: a cross-sectional study

Abstract Background Since the beginning of the family program in 1998, the proportion of married women who used contraception has fluctuated. An unmet need for contraception among women in Kyrgyzstan drastically increased from 2006 (1.1%) to 2014 (19.1%), and remained unchanged until 2018 (19.0%). This study aims to re-investigate the prevalence of an unmet need for contraception from 2006 to 2018 in a comprehensive manner, and examine the factors associated with an unmet need for contraception among married women over the course of 12 years in the Kyrgyz Republic. Methods This is a cross-sectional study using secondary data that derived from the Multiple Indicator Cluster Survey (MICS). The study employed three datasets from the MICS 2006, 2014, and 2018. The study included a total of 9,229 women aged 15–49 who were married and fecund, and whose status of the met/unmet need for contraception could be identified. Logistic regression was employed to estimate the relationship of an unmet need for contraception with independent factors. A P value < 0.05 was set as statistically significant. Results The prevalence of an unmet need for contraception was 19.9% in 2006, 20.4% in 2014, and 22.5% in 2018. Across 12 years, all reversible-contraceptive methods for women constantly declined. Although intrauterine devices were the prominent contraceptive method of usage among Kyrgyz women, the trend of usage drastically decreased over time. Factors associated with unmet need for contraception included women’s age, area of residence, mother tongue of household head, age of husband, and number of children ever born. Conclusion The unmet need for contraception among married Kyrgyz women slightly increased, and the trend of modern contraceptive usage declined from 2006 to 2018, particularly the use of pills, injections, and intra-uterine devices. Comprehensive sexual health education for young people and youth-friendly services should be promoted. An effective and reliable supply chain of contraceptive commodities should be prioritized and strengthened. Regular supportive supervision visits are essential to improve the knowledge and skills of healthcare providers to be able to provide intrauterine device service as a contraceptive choice for Kyrgyz women

Endometrioid Endometrial Carcinoma Indirectly Caused by Pituitary Prolactinoma:A Case Report

We present the case of a 44-year-old nulliparous woman who experienced irregular menstrual cycles for about 10 years and developed both pituitary prolactinoma and endometrioid endometrial carcinoma. In premenopausal women, hyperprolactinemia causes hypogonadism by inhibiting secretion of gonadotropin-releasing hormone and thus suppressing luteinizing hormone levels, which can cause menstrual disorders ranging from amenorrhea, oligomenorrhea and chronic anovulatory cycle to short luteal phase of the menstrual cycle. A chronic anovulatory menstrual cycle is the most common cause of long-term exposure of the endometrium to endogenous estrogen without adequate opposition from progestins, which can lead to endometrioid endometrial carcinoma. In this case, pituitary prolactinoma may have caused the chronic anovulatory cycle and indirectly led to the endometrioid endometrial carcinoma. In patients for whom the cause of irregular menstruation and chronic anovulatory cycle is suspected to be hyperprolactinemia, explorations of both the hypophysis and endometrium are essential