Methylation level of the RASSF1A promoter is an independent prognostic factor for clear-cell renal cell carcinoma.

BACKGROUND: Ras association domain family 1A (RASSF1A) is a tumor suppressor that regulates the cell cycle, apoptosis, and microtubule stability. The association between the methylation levels of RASSF1A and the prognosis of clear-cell renal cell carcinoma (CCRCC) remains unclear. Therefore, we investigated this relationship to determine the prognostic value of RASSF1A methylation levels for CCRCC. PATIENTS AND METHODS: The study comprised 179 Japanese patients who underwent radical or partial nephrectomy for CCRCC. The methylation level of 5' CpG islands in the RASSF1A was evaluated using combined bisulfite restriction analysis and bisulfite sequencing. RESULTS: High levels of methylation in the RASSF1A promoter were significantly more frequent in grade 3 compared with grade 1 or 2 tumors (P = 0.028) and in patients with stage III or IV compared with patients with stage I or II (P = 0.043). Patients with high methylation levels had a significantly less favorable prognosis compared with those with low methylation levels (P = 0.040). Higher methylation levels were independently associated with a poor prognosis following multivariate analysis (P = 0.0053). CONCLUSION: These results indicate that quantitative promoter methylation levels of the RASSF1A gene may be a useful marker to predict the prognosis of CCRCC.

Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells.

BACKGROUND: The canonical Wnt signalling pathway is activated in most sporadic colorectal cancers (CRCs). We previously reported that FZD7 functions as a receptor for the canonical Wnt signalling pathway in colon cancer cells. METHODS AND RESULTS: In this study, we examined the function of FZD7 in survival, invasion and metastatic capabilities of colon cancer cells. FZD7_siRNA transfection decreased cell viability of HT-29 and HCT-116 colon cancer cells. Expression of c-Jun, phosphorylation of JNK and c-Jun, and activation of RhoA were suppressed after FZD7_siRNA transfection into HCT-116 cells. In vitro invasion activity and Wnt target gene expression were also reduced in HCT-116 cells transfected with FZD7_siRNA. Liver metastasis of stable FZD7_siRNA HCT-116 cell transfectants in scid mice was decreased to 40-50% compared to controls. The mRNA levels of FZD7 in 135 primary CRC tissues were examined by real-time PCR. FZD7 mRNA levels were significantly higher in stage II, III or IV tumours than in non-tumour tissues (P<0.005), and overall survival was shorter in those patients with higher FZD7 expression (P<0.001). CONCLUSION: These data suggest that FZD7 may be involved in enhancement of survival, invasion and metastatic capabilities of colon cancer cells through non-canonical Wnt signalling pathways as well as the canonical pathway.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome after hematopoietic cell transplantation for lymphoma.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, P<0.001). Significant risk factors for the development of t-AML/MDS after autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.

Macrophage inflammatory protein 1alpha enhances in a different manner adhesion of hematopoietic progenitor cells from bone marrow, cord blood, and mobilized peripheral blood.

Regulatory mechanisms governing adhesion of hematopoietic progenitor cells to the stromal nische are poorly understood. Growth factors such as stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor, and thrombopoietin were reported to upregulate the adhesion of hematopoietic progenitors to immobilized fibronectin through activation of integrin alpha4beta1 and alpha5beta1. Macrophage inflammatory protein (MIP)-1alpha is a C-C chemokine that suppresses colony formation by stem/progenitor cells in vitro. We asked if MIP-1alpha would modulate the adhesive phenotype of colony-forming cells (CFCs) obtained from healthy donor bone marrow (BM), cord blood (CB), and mobilized peripheral blood (mPB) CD34+ cells, in comparison with SCF, using immobilized fibronectin. SCF significantly increased the level of adhesion of CFCs from BM, CB, and mPB. On the other hand, MIP-1alpha significantly increased the level of adhesion of CFCs from BM and CB, but less so from mPB. The effects of MIP-1alpha were inhibited by blocking antibodies to integrin alpha4, alpha5, or beta1, and polymerization plus rearrangement of F-actin were observed in affected cells by labeling with rhodamine-conjugated phalloidine. These data indicate that the effect of MIP-1alpha on the adhesive phenotype of CFCs is mediated by modulation of the organization of integrin. The amount of MIP-1alpha receptor on mPB was less than for BM or CB, which may explain the distinct characteristics in the adhesive response induced by MIP-1alpha. We suggest that hematopoietic progenitor cells from different sources may be heterogeneous with respect to maturation, integrin affinity, MIP-1alpha receptor expression, and regulation of MIP-1alpha signaling. Our data indicate that MIP-1alpha may affect migration, homing, and mobilization of hematopoietic progenitors by modulating the adhesive phenotype of these cells.

Conservation of the ID sequence and its expression as small RNA in rodent brains: analysis with cDNA for mouse brain-specific small RNA.

Two cDNA clones for mouse brain-specific small RNA were isolated, whose sequences turn out to be highly homologous to that of a genomic mouse ID-like clone isolated previously. By use of one of these cDNA clones as a probe, the copy numbers of ID-related sequences in several mammalian species were determined. The ID sequence was found to be conserved in mice, rats, hamsters and guinea pigs, but not in non-rodent species. There were about 3 orders of magnitude of difference in the copy numbers of the gene, i.e. rat 4.0 X 10(4), mouse 4.5 X 10(2), hamster 1.5 X 10(2), and guinea pig less than 50. The gene was transcribed as small RNA in the brain of rodent species. The relative concentration of small RNA in the brain was roughly proportional to the copy number of the ID sequence in mice, hamsters, and probably in guinea pigs also. On the other hand, the amount of the RNA in rat brain was much less than that expected from the large copy number of the gene. On the basis of these observations, the possibility is discussed that most of the ID sequences in the rat are pseudogenes.

Aberrant BCR-ABL transcript with intronic insertion in a patient with philadelphia chromosome-positive chronic myeloid leukemia: implications for disease progression.

The BCR-ABL fusion gene is important for the leukemogenesis of chronic myeloid leukemia (CML). A relationship between types of BCR-ABL transcripts in CML and clinical features has been proposed. We present here a patient with CML who carried an aberrant BCR-ABL transcript with an intronic sequence insert. A 26-year-old woman was diagnosed as having Philadelphia chromosome (Ph) positive CML. Reverse transcription polymerase chain reaction detected an atypically large BCR-ABL mRNA transcript. Sequencing revealed a 589bp insertion consisting of a 5' portion of BCR intron b2 and a 3' portion of ABL intron 1b between BCR exon b2 and ABL exon a2. Although the typical b2a2 transcript was undetectable initially, it appeared after intensive chemotherapy. The aberrant transcript presumably arose as a result of a lack of splicing, and chemotherapy might modify the disease course by selecting the subpopulation of the CML clone expressing typical BCR-ABL mRNA dominantly.

A case of 46,X,der(X)(pter-->q21::p21-->pter) with gonadal dysgenesis, tall stature, and endometriosis.

OBJECTIVE: To report a case of 46,X,der(X)(pter-->q21::p21-->pter) with gonadal dysgenesis, tall stature, and endometriosis. DESIGN: Case report. SETTING: A university hospital. PATIENT(S): A 20-year-old primary amenorrheal woman receiving estrogen-progestogen substitution. INTERVENTION(S): G-banding, comparative genomic hybridization, fluorescence in situ hybridization (FISH), and laparoscopy. MAIN OUTCOME MEASURE(S): A recombinant X chromosome, 46,X,der(X)(pter-->q21::p21-->pter), and pelvic endometriosis. RESULT(S): The patient's chromosomal abnormality was misjudged by the use of G-banding as a distal part deletion of the long arm in one X chromosome. Comparative genomic hybridization and fluorescence in situ hybridization analyses with locus-specific probes revealed 46,X,der(X)(pter-->q21::p21-->pter). The laparoscopic examination showed bilateral streak gonads and blue berry spots at the pelvic peritoneum, which were confirmed by evaluation of biopsy specimens. CONCLUSION(S): Recent advances of genetic strategies make it easy to determine karyotype and phenotype abnormalities. We have to keep our mind on the potential of endometriosis with patients who are receiving estrogen-progestogen substitution.

Anti-emetic effects of a novel NK-1 receptor antagonist HSP-117 in ferrets.

We have developed a non-peptide compound, HSP-117, antagonist of the tachykinin NK-1 receptor. Binding of 3H-substance P (SP) to the membranes of IM-9 cells was inhibited by the antagonists HSP-117 and CP-99,994, the inhibitory activity of HSP-117 being about 50-fold that of CP-99,994. The SP-induced firing responses of single neuron activity in slices of the nucleus tractus solitarius of ferrets were inhibited by 10 microM HSP-117. Intracerebroventricular injection of HSP-117 significantly inhibited retching and vomiting induced by copper sulphate and morphine and the inhibitory effect of HSP-117 on emesis was greater than that of CP-99,994. These results indicate that (1) HSP-117 is a potent anti-emetic agent, blocking NK-1 receptors in the nucleus tractus solitarius and (2) NK-1 receptors in the nucleus tractus solitarius play an important role in emesis induced by broad-spectrum emetic stimuli.

Electrophysiologic studies in an infant with Möbius syndrome.

The electrophysiologic findings in an infant with congenital facial diplegia (Möbius syndrome) are presented. As to serial electrically elicited blink reflexes, the R1 amplitude was significantly reduced and the R2 latency was significantly prolonged. The M response of the orbicularis oculi muscle showed slightly reduced amplitude. Auditory brainstem responses exhibited a prolonged time between waves I and V and reduced amplitude of wave V on the right side. Somatosensory evoked potentials and visual evoked potentials were normal. These findings suggest some degree of impairment of the peripheral facial nerve, and brainstem dysfunction including the pons and lateral medulla.

New molecular tumor markers for endometrial cancer.

Although the International Federation of Gynecology and Obstetrics officially changed the classification system of endometrial cancer from a clinically staged to a surgically staged disease in 1988, optimal management of patients with endometrial cancer is still controversial. Gynecologists happen to experience that patients with tumors that are identical in grade and stage often have significantly different clinical outcomes or responses to therapy. In order to identify an objective biological factor correlating with tumor aggressiveness, many tumor markers have been investigated. So far, CA125 is one of the most reliable tumor marker for adenocarcinoma of the uterus and frequently used in a clinical setting. Recently, with the advent of molecular biological techniques, many genes and regions of the genome related to endometrial cancer have been identified. We undertook a genome-wide screening to detect genetic changes by comparative genomic hybridization (CGH) in primary endometrioid cancers, since CGH analysis provides comprehensive information concerning relative chromosomal losses and gains in tumors by a single hybridization. In this paper, the usefulness of serum tumor markers and the new promising molecular tumor markers for endometrial cancer are discussed.

The excitability of blink reflexes in patients with neurologic and psychiatric disorders.

The blink reflex and its recovery curve were studied in 12 patients with neurologic and psychiatric disorders, i.e., juvenile Parkinson's disease (case 1), Gilles de la Tourette's syndrome (case 2), anorexia nervosa (case 3), mild developmental delay (cases 4 and 5), a meningomyelocele with winking spasms (case 6), Parkinson's disease (cases 7-10) and OPCA (cases 11 and 12). The cases were divided into 4 groups on the basis of the results, (1) hyperexcitability of facial motoneurons only (case 6), (2) hyperexcitability of facial motoneurons and brainstem interneurons (case 1 and 2), (3) hyperexcitability of brainstem interneurons only (cases 4, 5 and 7-12) and (4) hypoexcitability of both sides (case 3). Therefore, as to the excitability an abnormal pattern of blink reflexes could be a neurophysiologic marker of some neurologic and psychiatric disorders.

[Comparison between monotherapy with imipenem/cilastatin sodium (IPM/CS) and combinations of IPM/CS and other drugs for treating bacterial infections in patients with hematopoietic disorders].

One hundred and nine patients with infections concurrent with hematopoietic disorders were treated with imipenem/cilastatin sodium (IPM/CS) either alone (IPM/CS monotherapy) or in combination with other antimicrobial drugs (IPM/CS combination therapy). The following results were obtained. 1. One hundred and nine patients were allocated at random to two groups: 53 patients to IPM/CS monotherapy and 56 patients to IPM/CS combination therapy. Fourteen patients (6 and 8 in the 2 groups, respectively) were excluded from the clinical evaluation. There were not significant differences between the two groups with respect to the background. 2. The efficacy rates of the 2 treatments against bacterial infections were as follows: in the IPM/CS monotherapy group, 62.5% in 8 patients with sepsis, 75.0% in 23 patients with fever of undetermined origin (FUO), 50.0% in 10 patients with pneumonia, and 68.3% in the 47 patients, and in the IPM/CS combination group, 85.7% in 7 patients with sepsis, 63.6% in 24 patients with FUO, 50.5% in 8 patients with pneumonia, and 67.4% in the 48 patients. The differences between the two groups were not significant. 3. Among the drugs used in combination with IPM/CS, antibiotics other than penicillins, cephalosporins, and aminoglycosides were used in 12 patients and a high efficacy rate of 91.7% was obtained. 4. Bacteriologically, 19 and 17 strains were isolated from the IPM/CS monotherapy and combination therapy groups respectively, and the eradication rates were 100% and 88.9% respectively. 5. Side effects were noted in 2 patients in the IPM/CS monotherapy group and 7 in the combination therapy group, but all of these resolved after discontinuation or completion of the treatment. The efficacies against severe bacterial infections in the presence of hematopoietic disorders were not different between IPM/CS alone and IPM/CS in combination with other antibiotics. Adverse reactions were uncommon with the monotherapy.

[Donor leukocyte transfusion in a patient with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation: analysis of natural killer cell activity and T-cell receptor repertoire in bone marrow T cells that exhibited graft-versus-leukemia activity].

Hematologic relapse of chronic myeloid leukemia developed in 37-year-old man 255 days after allogeneic bone marrow transplantation. The patient received a donor lymphocyte transfusion (DLT) twice at a dose of 5 x 10(6)/kg T cells. He achieved complete cytogenetic response (CCR) 14 weeks after DLT, and has remained in a CCR state for 17 months. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. Natural killer (NK) cell activity was elevated. Also, analysis of the T cell receptor (TCR) repertoire disclosed oligoclonal expansion of T cells of the TCR V beta and J beta subfamilies. These observations provide evidence for the clonal expansion of allogeneic T cells that are capable of mediating antileukemic activity without causing GVHD.

[Bone marrow transplantation for a patient with ALL from her 75-year-old mother using cryopreserved bone marrow cells].

We report a 42-year-old woman with acute lymphoblastic leukemia who received allogeneic bone marrow transplantation (BMT) in the first remission from her 75-year-old, HLA-identical, MLC-non-reactive mother. Considering the difficulty to obtain a sufficient number of bone marrow cells from such an old donor, we harvested the cells (2.31 x 10(8)/kg) on day -37 and cryopreserved them until use. BMT was performed on June 3rd, 1993 after conditioning regimen with total body irradiation, high-dose AraC and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxisis was attempted by cyclosporin A and short-term methtrexate. Her hematopoietic recovery was favorable with no signs and symptoms of GVHD as far as day 218.

[Chlamydia pneumoniae infection in children with asthma exacerbation].

Little is known about the significance of C. pneumoniae in wheezing state in children. In this study, a total of 33 children with exacerbation of bronchial asthma were serologically and bacteriologically analyzed to investigate whether C. pneumoniae infection is associated with wheezing in children with bronchial asthma. 1) Of the 33 patients 12 (39%) had an acute antibody rise against C. pneumoniae. C. pneumoniae was isolated from 8 patients (24%) by culture. Based on these findings, 15 cases (45%) were diagnosed as C. pneumoniae infection. 2) There were no significant difference in clinical signs, symptoms and laboratory studies between with and without C. pneumoniae infection. The high incidence of C. pneumoniae infection in children with exacerbation of bronchial asthma suggests its significance as a cause of wheezing. Although there was no specific symptom in C. pneumoniae infection, this infection should be suspected in wheezing children for diagnosis and proper treatment.

[A case of severe milk allergy. Relationship with type I and Type III allergic reactions].

A case of cow's milk allergy related to type I and type III allergic reactions is reported. The patient is a one-month-old girl. She had watery diarrhea and abdominal distention soon after commencement of milk feeding two weeks after birth. She was cyanotic and floppy on admission. Intravenous complete hyperalimentation was tried to combat her diarrhea with good clinical effect. Then feeding with 605Z milk (enzyme digested cow's milk antigen, Meiji Milk Products Co., Ltd.) was started, and the diarrhea improved. Laboratory findings showed positive milk PK test, elevated IgE score, and positive milk specific RAST score, decreased serum complement, elevated levels of each immunoglobulin class of milk specific antibodies, especially milk specific IgG1 antibody and increased complement absorption test. She was diagnosed as having milk allergy related to both type I and type III allergies from the above-mentioned results. Specific antibodies were diminished after feeding with 605Z. Although her mother had not taken cow's milk over the past 10 years, she took a lot of milk during her pregnancy. But her serum milk specific antibodies were not elevated. It was suggested that the baby's antibodies were not derived from her mother but that the baby produced them by herself.

[Development of a system for monitoring the production of leukotriene B4, C4, D4 and E4 in whole blood of pediatric asthmatic patients].

We have developed a new method using a computerized photodiode-array spectrophotometer (CPAS), to characterize the biosynthesis and the inhibition of leukotriene (LT) B4, C4, D4 and E4 in calcium ionophore (Ca-I)-stimulated whole blood. The results obtained were as follows: 1. The use of CPAS enabled us to identify and measure LTs from 2 ml volume of Ca-I stimulated whole blood as well as to check the purity of LTs, without any use of radioimmunoassay or bioassay. 2. LTC4 produced in whole blood was almost completely converted to LTE4 after 80 min incubation, and at this time both the production of LTE4 and LTB4 reached a plateau and remained constant thereafter. 3. Azelastine added in vitro caused a dose-dependent inhibition of Ca-I stimulated LTB4 and LTE4 production with an IC50 of 10 microM.

[Photodynamic therapy (PDT) for early cervical cancer].

The incidence of carcinoma in situ (CIS) and dysplasia of the uterine cervix has been increasing among young women in recent years. Most of these patients want to preserve their fertility. Also, to accommodate high-risk patients with complications, elderly patients, and those who refuse surgery, we perform PDT as a method to preserve fertility. The technique required for PDT is relatively simple, and can be performed without anesthesia, since it causes no pain or bleeding. PDT, with the use of Excimer Dye Laser (EDL), a type of low pulse laser, has a considerably higher degree of tissue penetration, even compared to PDT using Argon Dye Laser (ADL). Also, PDT using EDL can manage glandular involvement of CIN, and its special feature of selective destruction of malignant cells with almost no effect on normal tissues is noteworthy. Beginning in 1995, PDT using YAG-OPO Laser with a variable laser wavelength has been performed. PDT is performed 48 hours after intravenous injection of 1.5 mg/kg to 2 mg/kg photosensitizer Porfimer sodium (PHE) when the difference in density of PHE becomes greatest between malignant cells and normal tissue. The most advanced features of our method compared to conventional radiation which uses cut fiber are: First, by using colposcope with an optical path for the laser, it is possible to show a 10 mm circular spot at the focus of observation. With this method, cervical lesions can be observed and checked while receiving stable and precise photoradiation by using colposcope through direct observation. Second, for cervical canal treatment, by using a cervical probe to administer photoradiation in the forward direction in the cervical canal and to the side walls, 70% of the laser light is scattered to the side walls, so that all of the cervical canal can be radiated. Also, the cervical canal probe used to administer photoradiation, by inserting 2 cm to 3 cm depending on the conditions of the cervical canal and withdrawing the probe 1 mm, can be performed precisely and promptly by using the cervical probe manipulator feature of the colposcope. At the present time, studies using the PDT method have been conducted on 56 patients (39 CIS and 17 dysplasia patients). Out of these 56 patients, there were 54 CR (96.4%), only one NC, and one PR with very limited remnants but most of the lesions had disappeared. The NC was highly suspected to be invasive carcinoma and the PR was CIS. In the CIS case, some remnant was evident at the end of the cervical canal, and PDT was administered again. After this treatment, it became CR. This was 10 months ago, and no abnormal condition has been reported since. The first CR case was reported 6 years ago among the 56 cases studied, and no recurrence has been observed to date. Five patients became pregnant after the treatment. Four had normal deliveries and one had a cesarean section. PDT's side effect is similar to symptoms of sunburn such as minor skin irritation due to sensitive reaction to sunlight. Normally, it can be relieved by applying carmine lotion, and even cases that required treatment were cured completely within a few days after applying steroid ointment. Before hospitalization, if the patient gets a sunburn from being outside, the sensitive reaction to laser light is almost nonexistent. Thus, we advise patients to get some exposure to the sun before being hospitalized. Also, in cases where strict shading time is observed, side effects are not apparent at all, and no abnormal findings are recognized in the blood and urine due to using PHE. With almost no side effects, bleeding or pain, and with certain improvements in administration methods, a better choice of photosensitizer which would shorten the shading time, PDT is considered to be the best therapy for treating CIS and dysplasia while preserving fertility.

[Cancer-associated gene abnormalities and chemosensitivity].

One of the most important clinical issues in cancer chemotherapy is the presence of intrinsic resistance or the appearance of acquired resistance against chemotherapy. As for intrinsic resistance, we had to perform direct chemo-sensitivity testing, or had to rely on the knowledge empirically acquired from randomized clinical trials. However, molecular or genetic markers associated with chemo-sensitivity have been reported recently. For example, inactivation of p53 or GML gene has been reported to be associated with chemo-resistance. Overexpression of topo-isomerase I has been reported to be associated with chemo-sensitivity to Topo I inhibitor. Overexpression of Thymidine Phosphorylase has been found to be associated with chemo-sensitivity to prodrug of 5-FU. By checking the status of such chemo-sensitivity markers prior to chemotherapy, it would be possible to predict the chemotherapeutic effect and even the necessity of the chemotherapy in the near future. In this article, we review the chemo-sensitivity markers reported so far, and methodology contributing to the discovery of new chemo-sensitivity markers. As a clinical study, 11 cases of ovarian cancer with high sensitivity to cisplatin-based chemotherapy and 29 cases of ovarian cancer with chemoresistance were analyzed by Comparative Genomic Hybridization (CGH). Copy number decrease in Xp, and copy number increase in 19q were observed in 13, 12 out of 29 resistant cases (45, 41%) and zero, 1 out of 11 sensitive cases (0, 9%), suggesting that -Xp and +19q were likely to be a genetic event associated with intrinsic drug-resistance (p = 0.006, 0.05, respectively). This effort should contribute to the discovery of new chemo-sensitivity and resistance markers.

[CGH (comparative genomic hybridization)].

Comparative Genomic Hybridization (CGH) is a powerful new method which allows genome-wide mapping of regions with DNA sequence copy number changes (both increases and decreases) in a single experiment without previous knowledge of the locations of the regions of abnormality. CGH is based on in situ hybridization of differentially labeled total genomic tumor DNA and normal DNA to normal human metaphase chromosomes. After hybridization copy number variations among the sequences in the tumor DNA are detected by measuring the tumor/normal fluorescence intensity ratio for each locus in the target chromosomes. Many previously unknown chromosomal regions with relative copy number changes have been detected in various tumors by CGH. Some changes have been identified as genetic markers associated with biological and clinico-pathological characteristics (i.e., histopathological grade, and clinical outcome). We review the published CGH articles and discuss briefly on current progress in CGH analysis to ovarian and uterine cervical cancer in our laboratory.