Shozo Yoshida

Nara Medical University, Nara, Nara, Japan

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Publications (34)56.71 Total impact

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    ABSTRACT: A 32-year-old gravid 1, parity 0 woman was referred to our hospital with suspicion of ectopic pregnancy 31 days after her previous menstrual period. She had a 5-month history of secondary infertility reported increasing lower abdominal pain. Her serum human chronic gonadotropin level was 8160 mIU/mL. Her medical history was significant for a myomectomy and an enucleation of left ovarian cyst. On suspicion of an ectopic pregnancy, laparoscopic exploration was performed. Dense pelvic adhesion was seen. After dissection of the adhesion, we could not find the blastocyst in her pelvis. Early pregnancy tissue implanted in the omentum was identified and was excised laparoscopically. The postoperative course was uneventful. When no ectopia is found in the fallopian tubes during laparoscopy or laparotomy for ectopic pregnancy, all peritoneal surfaces and the omentum must be carefully inspected during surgery.
    Asian Journal of Endoscopic Surgery 11/2013; 6(4):327-9.
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    ABSTRACT: Inflammation plays a role in the pathogenesis of endometriosis. Endometriosis-associated ovarian carcinogenesis might be promoted through oxidative stress-induced increased genomic instability, aberrant methylation, and aberrant chromatin remodeling, as well as mutations of tumor suppressor genes. Aberrant expression of ARID1A, PIK3CA, and NF-kB genes has been recognized as the major target genes involved in oxidative stress-induced carcinogenesis. HNF-1beta appears to play a key role in anti-oxidative defense mechanisms. We discuss the pathophysiologic roles of oxidative stress as somatic mutations as well as highly specific agents that effectively modulate these targets.
    Cancer Investigation 04/2012; 30(6):473-80. · 2.24 Impact Factor
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    ABSTRACT: Inflammatory response in preeclampsia (PE) is a key feature in its pathophysiology. Advanced Glycation Endproducts (AGEs), receptors for AGEs (RAGE), and RAGE ligands are involved in systemic inflammation in various pathological conditions. In this study, we measured serum RAGE ligands in normal pregnancy controls and PE patients. Levels of Carboxymethyl Lysine (CML), HMGB1 and S100A12/EN-RAGE were measured in thirty-three normal pregnant women 3 times at 10-12 (1st measurement), 28 (2nd measurement), and 36 (3rd measurement) weeks during gestation for paired analysis. We also measured those in serum samples from 17 severe PE patients at admission using ELISA. Early onset (EO, <32 weeks) and late onset (LO, ≥32 weeks) PE patients were compared with the 2nd and 3rd measurements of normal controls, respectively. CML and HMGB1 did not change during normal pregnancy. However, S100A12/EN-RAGE decreased from the 1st to 2nd measurement (P<0.0001). Across all PE patients, serum CML was unaltered, while HMGB1 significantly increased compared to 2nd (P=0.0002) and 3rd (P<0.0001) measurement as well as individually compared to both EO (P=0.018) and LO groups (P=0.0001). S100A12 in all PE patients increased over 2nd (P=0.0015) and 3rd (P=0.0002) measurements, although only LO was significantly increased compared to the 3rd measurement (P=0.0005). Our data suggest that patterns of serum RAGE ligand concentration indicate different inflammatory pathways in normal pregnancy, EO-PE, and LO-PE.
    Journal of Reproductive Immunology 02/2012; 93(2):69-74. · 2.34 Impact Factor
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    ABSTRACT: We report a case of ovarian carcinoid tumor that recurred with multiple liver metastases and was successfully treated with chemoembolization. A 76-year-old woman was admitted to our hospital presented with abdominal distension and abnormal uterine bleeding for about 6 months. She presented with hyperestrogenic and androgenic manifestations such as vaginal bleeding with endometrial hyperplasia and hirsutism. Magnetic resonance (MR) imaging revealed a large solid and cystic ovarian tumor of 17 cm at maximum diameter. On the basis of the clinical diagnosis of sex cord stromal tumor containing a mature cystic teratoma, she underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The pathology report revealed that the mass in the left ovary was a carcinoid tumor, insular type, with mature cystic teratoma. Two years after surgical treatment, multiple liver metastases were revealed by abdominal CT. Hepatic arterial infusion of cisplatin was performed for 2 courses, and multiple metastatic nodules have remarkably reduced. No established chemotherapy or radiation therapy treatments are currently available for recurrent or advanced carcinoid tumors. Our paper suggests that chemoembolization with cisplatin may be effective in treatment of patients with multiple liver metastases of ovarian carcinoid tumor.
    Case reports in obstetrics and gynecology. 01/2012; 2012:961087.
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    ABSTRACT: Two histologic types, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC), are the common histology in ovarian cancer patients who have associated endometriosis. However, both tumor types have distinct clinicopathological characteristics and molecular phenotypes. EAC is predominantly positive for estrogen receptor (ER), but CCC specifically exhibits lower ER expression. This study reviews the current understanding of the role of the ER information in the pathogenesis of CCC, as well as the English language literature for biochemical studies on ER expression and estrogenic action in CCC. The iron-mediated oxidative stress occurs due to repeated hemorrhage in endometriosis, then this compound oxidatively modifies genomic DNA and, subsequently, ER depletion may be observed. There are a number of factors that interfere with ER expression and estrogen activity, which include DNA methylation of the promoter region, histone deacetylation, heme and iron binding, chromatin remodeling and ubiquitin ligase activity. Loss of estrogen function may be a turning point in CCC progression and aggressiveness.
    Experimental and therapeutic medicine 01/2012; 3(1):18-24. · 0.34 Impact Factor
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    ABSTRACT: This review summarizes data from recent molecular genetic and epidemiology studies of the generic term 'female pelvic cancer'. The English-language literature was reviewed for genetic, epigenetic, epidemiologic and environmental risk factors. There are well-documented disparities among racial and ethnic groups with respect to epithelial ovarian cancer (EOC) prevalence. In the case of the serous histological subtype, primary EOC, fallopian tube cancer and peritoneal cancer could be regarded as a single disease entity. However, EOC is not a single disease. Comparing the profile of EOC between Japanese and Caucasians, clear cell carcinomas (27.6%) are more common in Japan, possibly with fewer serous adenocarcinomas (40.7%). This may reflect a proportional increase. The Japanese may exhibit a higher proportion of malignant transformation of endometriosis compared to the United States population. Although some part of the molecular genetic pathogenesis has been unveiled, the complete events of molecular genetic epidemiological changes associated with EOC remain to be identified. This review focuses on current knowledge of the genetic and environmental factors affecting the development of EOC, and outlines future challenges in its pathogenesis research.
    Oncology Reports 09/2011; 26(6):1347-56. · 2.30 Impact Factor
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    ABSTRACT: Epithelial ovarian cancer (EOC) is the most lethal pelvic gynecologic cancer. Clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) of the ovary have been associated with endometriosis, thus indicating that endometriosis has been believed to increase the risk of developing EOC. The aim of our review was to identify and synthesize the most current information on CCC with regard to molecular and pathophysiological distinctions. This article reviews the English-language literature for molecular, pathogenetic, and pathophysiological studies on endometriosis and endometriosis-associated ovarian cancer (EAOC). In this review, we focus on the functions and roles of redox-active iron in CCC carcinogenesis. The iron-induced reactive oxygen species signals can contribute to carcinogenesis via 3 major processes: step 1, by increasing oxidative stress, which promotes DNA mutagenesis, histone modification, chromatin remodeling, and gene products activation/inactivation thus contributing to EAOC initiation; step 2, by activating detoxification and antiapoptotic pathways via the transcription factor hepatocyte nuclear factor 1β overexpression, thereby contributing to CCC promotion; and step 3, by creating an environment that supports sustained growth, angiogenesis, migration, and invasion of cancer cells via estrogen-dependent (EAC) or estrogen-independent (CCC) mechanisms, thus supporting tumor progression and metastasis. These aspects of reactive oxygen species biology will be discussed in the context of its relationship to EAOC carcinogenesis.
    International Journal of Gynecological Cancer 08/2011; 21(7):1200-7. · 1.94 Impact Factor
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    ABSTRACT: Recent data have provided information regarding the profiles of clear cell carcinoma of the ovary (CCC) with adenine-thymine rich interactive domain 1A (ARID1A) mutations. The purpose of this review was to summarize current knowledge regarding the molecular mechanisms involved in CCC tumorigenesis and to describe the central role played by the aberrant chromatin remodeling. The present article reviews the English-language literature for biochemical studies on the ARID1A mutation and chromatin remodeling in CCC. ARID1A is responsible for directing the SWI/SNF complex to target promoters and regulates the transcription of certain genes by altering the chromatin structure around those genes. The mutation spectrum of ARID1A was enriched for C to T transitions. CCC and clear cell renal cell carcinoma (ccRCC) resemble each other pathogenetically. Dysfunction of the ARID1A protein, which occurs with VHL mutations in ccRCC, is responsible for loss of the assembly of the ARID1A-mediated histone H2B complex. Therefore, ARID1A acts as a chromatin remodeling modifier, which stimulates cell signaling that can lead to cell cycle arrest and cell death in the event of DNA damage. The dysfunction of ARID1A may result in susceptibility to CCC carcinogenesis through a defect in the repair or replication of damaged DNA.
    Oncology letters 07/2011; 2(4):591-597. · 0.24 Impact Factor
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    ABSTRACT: Hepatocyte growth factor (HGF) is up-regulated in tissue repair and has been implicated in playing a role in this process through its anti-apoptotic and proliferative activities. Cyclooxygenase-2 (COX-2) is an inducible enzyme in the biosynthetic pathway of prostaglandins, and its activation has been shown to play an important role in cell growth. We previously reported that HGF significantly inhibited anoikis, possibly through the up-regulation of COX-2 expression in the endometrial RL95-2 cancer cell line. Here, we report that i) treatment of RL95-2 cells with HGF resulted in phosphorylation of the HGF receptor c-Met, activation of Akt and IκB, translocation of NF-κB into the nucleus, and up-regulation of COX-2 mRNA; ii) the IκB-α phosphorylation inhibitor BAY11-7082 and the selective COX-2 inhibitor CAY10452 blocked HGF-mediated anoikis resistance in RL95-2 cells; and iii) HGF induced migration and invasion in RL95-2 cells, while the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and CAY10452 blocked these effects of HGF stimulation. Our data suggest that HGF possesses chemotactic ability, has anti-apoptosis action, and induces cellular infiltration via the PI3K/Akt pathway; it also triggers NF-κB activation and up-regulates COX-2 gene expression in endometrial cancer cells.
    Oncology Reports 06/2011; 26(4):957-64. · 2.30 Impact Factor
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    ABSTRACT: Although metastasis to the bone is common in solid tumors, it seldom occurs in endometrial cancer. A rare case of endometrial carcinoma that presented wth symptoms of bone metastasis in the right ischium and treated successfully by zoledronic acid is described. A 57-year-old woman presented with pain of the right ischium. Computed tomography and magnetic resonance imaging revealed bone metastasis and enlargement of the uterus. Endometrial biopsy confirmed endometrial adenocarcinoma. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and biopsy of the ischium. Postoperatively, the patient received six courses of chemotherapy using paclitaxel and carboplatin. However, pain of the right-ischium reappeared 9 months after surgery. The patient was treated with 4 mg of zoledronic acid every 4 weeks. After 4 cycles of treatment, the visual analogue scale regressed from 70 to 10. Zoledronic acid can palliate bone pain caused by a variety of endometrial cancers.
    Gan to kagaku ryoho. Cancer & chemotherapy 06/2011; 38(6):1035-8.
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    ABSTRACT: Preeclampsia, a pregnancy-specific hypertensive syndrome, is one of the leading causes of premature births as well as fetal and maternal death. Preeclampsia lacks effective therapies because of the poor understanding of disease pathogenesis. The aim of this paper is to review molecular signaling pathways that could be responsible for the pathogenesis of preeclampsia. This article reviews the English-language literature for pathogenesis and pathophysiological mechanisms of preeclampsia based on genome-wide gene expression profiling and proteomic studies. We show that the expression of the genes and proteins involved in response to stress, host-pathogen interactions, immune system, inflammation, lipid metabolism, carbohydrate metabolism, growth and tissue remodeling was increased in preeclampsia. Several significant common pathways observed in preeclampsia overlap the datasets identified in TLR (Toll-like receptor)- and RAGE (receptor for advanced glycation end products)-dependent signaling pathways. Placental oxidative stress and subsequent chronic inflammation are considered to be major contributors to the development of preeclampsia. This review summarizes recent advances in TLR- and RAGE-mediated signaling and the target molecules, and provides new insights into the pathogenesis of preeclampsia.
    Agents and Actions 03/2011; 60(6):509-20. · 1.59 Impact Factor
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    ABSTRACT: In the ovary, clear cell carcinoma (CCC) and endometrioid adenocarcinoma occur in the setting of endometriosis. In this review, we discuss the role of innate immune responses, specifically endogenous ligands (also known as "alarmins"), their pattern recognition receptors (PRRs) and their signaling pathways, in the pathogenesis of ovarian cancer, in particular, endometriosis-associated ovarian cancer. This article reviews the English-language literature for pathogenesis and pathophysiological studies on endometriosis and ovarian cancer. Here, we show that iron functions as an endogenous ligand and can induce chromosomal instability through production of reactive oxygen intermediates-induced oxidative stress. Several important CCC-related genes overlap with those known to be associated with hepatocyte nuclear factor-1β-dependent oxidative stress. Aberrant expression of PRRs and HNF-1β in endometriosis has been reported in the setting of chronic inflammation and oxidative stress pathways, which lie downstream of these genes. A concerted overexpression of alarmins, their receptors and HNF-1β might be required for endometriosis carcinogenesis. Recent advances in innate immunity illuminate the molecular mechanism underlying inflammation-induced carcinogenesis. Upregulation of PRRs expression may synergize with activation of HNF-1β signaling to accelerate endometriosis proliferation and cause carcinogenesis.
    Human immunology 03/2011; 72(3):213-8. · 2.55 Impact Factor
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    ABSTRACT: Various theories try to explain the development and progression of endometriosis, however, no single theory can explain all aspects of this disorder. Gene expression profiling studies might reveal factors that explain variability in disease development and progression, which can serve as specific biomarkers for endometriosis and novel drug development. We have recently showed that the upregulated genes were predominantly clustered in stress and detoxification, providing a mechanistic explanation for the oxidative stress and chronic inflammatory response in endometriosis. This review aims: (1) to analyse the published data, with the aim of identifying pathways consistently regulated by the endometriosis genotype and (2) to summarise the findings of specific genes, which are involved in the process of oxidative stress and inflammation. We identified gene array and proteomics studies whose data were accessible in PubMed. A major finding is the increased expressions of several markers including heat shock protein, S100, fibronectin, and neutrophil elastase, which might be involved in the process of Toll-like receptor (TLR)-dependent sterile inflammation. The study reviews a convergence in the main pathogenic process, where the TLR-mediated inflammation occurs possibly through the endogenous ligands. In conclusion, a circulus vitiosus of both the oxidative stress pathway and the TLR pathways is generated when the process becomes chronic (danger signal spiral).
    Gynecological Endocrinology 02/2011; 27(2):73-9. · 1.30 Impact Factor
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    ABSTRACT: Endometriosis affects an estimated 10% of women in the reproductive-age group. Here, we review current knowledge on molecular genesis of endometriosis-associated epithelial ovarian carcinoma (EOC). This article reviews the English language literature for biology, pathogenesis, and pathophysiological studies on endometriosis-associated EOC. Although endometriosis generally remains a benign condition, it demonstrates somatically acquired genetic alterations. Clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) are the most frequent types of EOC associated with endometriosis. Retrograde menstruation or ovarian hemorrhage carries highly pro-oxidant factors, such as iron, into the peritoneal cavity or ovarian endometrioma. CCC and EAC should be considered separately in studies of endometriosis-associated EOC. The repeated events of hemorrhage in endometriosis can contribute to carcinogenesis and progression via 3 major processes: 1) increasing oxidative stress promotes DNA methylation; 2) activating anti-apoptotic pathways supports tumor promotion; and 3) aberrant expression of stress signaling pathways contributes to tumor progression. This review summarizes recent advances in the understanding of epidemiology, carcinogenesis, pathogenesis, and pathophysiology of endometriosis-associated EOC; and a possible novel model is proposed.
    Frontiers in bioscience (Elite edition) 01/2011; 3:529-39.
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    ABSTRACT: Aims: Up to 10% of pregnant women have preterm birth that might be refractory to current therapy. Infections and asphyxia related to preterm birth are the causes of death in the majority of neonates and therefore represent an urgent clinical need. Methods: The present article reviews the English language literature for preclinical and clinical trials and promising molecular targets on preterm labor. Results: Preterm birth is a complex heterogeneous condition. There is no current treatment for the fetal membranes once they have ruptured; therefore, essentially any treatment has to be preventative to quiesce preterm labor and prevent any spread of infection to the fetus. Modulating the pro-inflammatory process-mediated cytokine network may present a new paradigm for preterm labor treatment. There are many reports on the role of β-adrenergic agonists (betamimetics), magnesium sulfate, progesterone, oxytocin antagonist, calcium channel blocker or the Kunitz inhibitor bikunin in the treatment of preterm labor. In the present review, we have focused on the preclinical and clinical anticytokine therapy for preterm labor. The preclinical and clinical trials with bikunin reducing preterm labor exacerbations have raised the importance of usefulness and safety considerations related to this novel therapy. Conclusion: Anticytokine therapy is ready for the clinic.
    Gynecologic and Obstetric Investigation 01/2011; 71(1):1-10. · 1.10 Impact Factor
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    ABSTRACT: We studied the potential use of sentinel lymph node identification using a near-infrared fluorescence imaging technique in the treatment of cervical cancer. Directly before the start of the operation, 0.2 ml of 5 mg/ml indocyanine green was prepared and injected into 4 sites in the cervix using a 26-gauge standard needle, at 3, 6, 9 and 12 o'clock positions. When the operation was advanced to the pelvis, near-infrared fluorescence imaging was performed using photodynamic eye (Hamamatsu Photonics Co., Japan). The sentinel lymph nodes and other dissected lymph nodes were histologically examined to find any metastases. Twelve patients were examined. Their ages ranged from 36 to 68 years (median, 58). Sentinel lymph nodes were identified in 10 patients (83%), and all were bilaterally identified. The median maximum tumor diameter of dissected cervical tumors was 35 mm (22-65); histology was squamous cell carcinoma in 8 patients and adenocarcinoma in 2 patients. Capillary lymphatic space involvement was found in 8 of the 10 patients. The site of the sentinel lymph node was the right external iliac node in 8 patients, the right obturator node in 8, the left external iliac node in 9, and the left obturator node in 8. Lymph node metastasis was found in 2 of the 12 patients, and all were sentinel lymph nodes. No metastasis from lymph nodes other than sentinel lymph nodes was observed. Photodynamic eye achieved a detection rate similar to that obtained with the blue dye and radioisotope method. It is also easier to use than the other two methods.
    Tumori 06/2010; 96(6):936-40. · 0.92 Impact Factor
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    ABSTRACT: Protease inhibitors, including the Kunitz, Kazal, serpin and mucus families, play important roles in inhibiting protease activities during homeostasis, inflammation, tissue injury, and cancer progression. Interestingly, in addition to their anti-protease activity, protease inhibitors also often possess other intrinsic properties that contribute to termination of the inflammatory process, including modulation of cytokine expression, signal transduction and tissue remodeling. In this review we have tried to summarize recent findings on the Kunitz family of serine proteinase inhibitors and their implications in health and disease. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to October 2009. We tried to limit the review to anti-inflammatory actions and actions not related to protease inhibition. Recent studies have demonstrated that the Kunitz inhibitors are not only protease inhibitors, but can also prevent inflammation and tissue injury and subsequently promote tissue remodeling.
    Agents and Actions 05/2010; 59(9):679-87. · 1.59 Impact Factor
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    ABSTRACT: Epithelial ovarian cancer (EOC) is the most common cause of gynecological cancer-related mortality. Clear cell EOC (cEOC) has a number of clinical features distinguishing it from other EOC because of frequent concurrence of endometriosis and highly chemoresistant nature resulting in a poor prognosis. Recent biochemical studies based on genome-wide expression analysis technology have noted specific expression of a transcription factor, hepatocyte nuclear factor-1beta (HNF-1beta), in cEOC and genetic alteration may be involved in oxidative stress. We describe the HNF-1beta-dependent pathophysiology of cEOC and discuss its role in oxidative stress-induced carcinogenesis. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2009, combining the keywords, genome-wide, microarray, epithelial ovarian cancer, clear cell carcinoma, oxidative stress, and detoxification, with specific expression profiles of genes. The catalog of cEOC-specificity might be a manifestation of six essential alterations in cell physiology: oxidative stress and detoxification, proteases, signal transduction, adhesion, transcription, and metabolism. Among 54 genes highly upregulated in cEOC, 47 genes (87.0%) were associated with the redox-related genes. Several important cEOC-related genes overlap with those known to be regulated by HNF-1beta. Twenty-two (40.7%) of the 54 genes predominantly identified in cEOC were involved in downstream targets of HNF-1beta. The HNF-1beta-dependent pathway might provide new insights into regulation of glycogen synthesis, detoxification and resistance to anticancer agents. This review summarizes recent advances in the understanding of oxidative stress and antioxidant mechanisms in pathogenesis of cEOC. A redox-sensitive subset of cEOC genes linked to oxidative and detoxification pathways was identified and associated with HNF-1beta-specific downstream targets.
    Oncology Reports 05/2010; 23(5):1193-203. · 2.30 Impact Factor
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    ABSTRACT: Individuals with inflammation have a myriad of pregnancy aberrations including increasing their preterm birth risk. Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) and their ligands were all found to play a key role in inflammation. In the present study, we reviewed TLR and RAGE expression, their ligands, and signaling in preterm birth. A systematic search was performed in the electronic databases PubMed and ScienceDirect up to July 2010, combining the keywords "preterm birth," "TLR", "RAGE", "danger signal", "alarmin", "genomewide," "microarray," and "proteomics" with specific expression profiles of genes and proteins. This paper provides data on TLR and RAGE levels and critical downstream signaling events including NF-kappaB-dependent proinflammatory cytokine expression in preterm birth. About half of the genes and proteins specifically present in preterm birth have the properties of endogenous ligands "alarmin" for receptor activation. The interactions between the TLR-mediated acute inflammation and RAGE-mediated chronic inflammation have clear implications for preterm birth via the TLR and RAGE system, which may be acting collectively. TLR and RAGE expression and their ligands, signaling, and functional activation are increased in preterm birth and may contribute to the proinflammatory state.
    Mediators of Inflammation 01/2010; 2010:490406. · 3.88 Impact Factor
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    ABSTRACT: Among epithelial ovarian cancer (EOC), clear cell carcinomas (CCC) differ from the other histologic types with respect to their clinical characteristics, carcinogenesis and prognosis. The aim of this review is to summarize the current knowledge and future perspective on the new therapeutic targets and treatment strategies for CCC. The present article reviews the English language literature for preclinical and clinical trials and promising molecular targets on CCC of the ovary, based on the gene expression profiling studies. Here, we show that (1) the expression of the genes involved in transcription, signaling, cell cycle, adhesion, matrix, proteinase, and detoxification was greatly increased in the CCC carcinogenesis; (2) upregulation of hepatocyte nuclear factor-1beta (HNF-1beta) and Polo-like kinase (PLK)-Early mitotic inhibitor-1 (Emi1) as well as their downstream targets are specifically found in most CCC. The promising molecular targeting approach will emerge in the context of HNF-1beta and PLK-Emi1 biology; and 3) several significant common pathways observed in CCC of the ovary overlap the datasets identified in CCC of the kidney. To improve the outcome in CCC therapy, we must learn various adaptive treatment strategies for renal CCC, although it is not supported by any preliminary clinical data. The inhibitors that target HNF-1beta and PLK-Emi1 and their downstream signaling molecules would be evaluated. In addition, the therapy currently used in renal CCC should be considered as an alternative for the present treatments or an attractive therapeutic option for ovarian CCC. The challenges accompanying the recent advance are described in this review article.
    Cancer Treatment Reviews 09/2009; 35(7):608-15. · 6.02 Impact Factor