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Biomedical subjects

J Ro

Publications and source records attributed to J Ro.

At least 19 recordsLinked to original sources
PubMed2006

Serum HER-2 concentration in patients with primary breast cancer.

OBJECTIVE: To evaluate whether serum HER-2/neu (HER-2) concentration is a valid index of HER-2 status in women with primary breast cancer, and to establish a normal reference range for serum HER-2 concentration in Korean women. METHODS: Serum HER-2 concentration was measured and immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) carried out on tissue samples from 86 consecutive female patients. The results of the three datasets were compared. The cut off value of HER-2 concentration was determined from the mean +2SD values derived from the serum of 93 healthy volunteers. RESULTS: The IHC and FISH data were significantly correlated (p<0.01), but neither showed significant correlation with the serum HER-2 data. The cut off value of serum HER-2 was 10.2 microg/l, and the serum HER-2 concentration of patients with primary breast cancer ranged from 5.0 to 17.5 microg/l. Only five patients had a serum HER-2 value above the cut off value. CONCLUSIONS: Serum HER-2 concentration cannot be substituted for IHC or FISH to evaluate HER-2 status, nor can it be used as a diagnostic tumour marker in primary breast cancer, considering the low prevalence of serum HER-2 elevation.

Adult↗
PubMed2004

Predictive value of [18F]FDG PET for pathological response of breast cancer to neo-adjuvant chemotherapy.

BACKGROUND: The aim of this prospective study was to evaluate the predictive value of [18F]fluorodeoxyglucose positron emission tomography (FDG PET) for the pathological response of breast cancer after completion of neo-adjuvant chemotherapy. METHODS: Fifty patients with newly diagnosed, non-inflammatory, large or locally advanced breast cancer undergoing neo-adjuvant chemotherapy were eligible for this study. Clinical assessment was accomplished by comparing initial tumor size with preoperative tumor size. Pathological responses were classified into three groups: pathological non-response (pNR), pathological partial response (pPR) and pathological complete response (pCR). To determine the effect of reduction rate (RR) of peak standardized uptake values for tumor responses, logistic regression analyses were performed. To identify an optimal threshold value of RR for the prediction of pathological response, receiver operating characteristic analysis was performed. RESULTS: Eight per cent (four of 50) of the patients had pCR and 46% had pPR. Ten per cent of patients had clinical CR and 52% had clinical PR. In clinical response, the RRs (+/- SD) of CR (-83.4 +/- 12), PR (-81.8 +/- 22.7) and NR (-79.7 +/- 31.9) showed no statistical differences (P > 0.05). However, for pathological responses, the RR of CR (-96.5 +/- 3.4) had a lower value than those of PR (-87.9 +/- 15.1) and NR (-56.2 +/- 29.6) (P = 0.0006; CR versus PR, P < 0.05; CR versus NR, P < 0.05; PR versus NR, P < 0.01). When -88% of RR was used as threshold value for differentiation between pCR and pPR, the area under the curve (AUC) was 0.788 [standard error (SE) 0.106; 95% confidence interval (CI) 0.589-0.920]. The sensitivity and specificity were 100% and 56.5%, respectively. When -79% of RR was used as threshold value for differentiation between pathological responders and non-responders, the AUC was 0.838 (SE 0.059; 95% CI 0.707-0.927). The sensitivity and specificity were 85.2% and 82.6%, respectively. CONCLUSIONS: Despite some limitations, this study suggests a possible predictive value of FDG PET for the assessment of the pathological response of primary breast cancer after neo-adjuvant chemotherapy. However, these findings deserve further investigation on a larger number of patients, and more frequent and earlier PET scans in each patient need to be performed to allow a better validation of the differentiation between the responder and non-responder groups.

Adult↗
PubMed2002

Randomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II-III non-small cell lung cancer: preliminary results.

A prospective randomized study was conducted to determine whether amifostine (Ethyol) reduces the rate of severe esophagitis and hematologic and pulmonary toxicity associated with chemoradiation or improves control of non-small cell lung cancer (NSCLC). Sixty patients with inoperable stage II or III NSCLC were treated with concurrent chemoradiotherapy. Both groups received thoracic radiation therapy (TRT) with 1.2 Gy/fraction, 2 fraction per day, 5 days per week for a total dose 69.6 Gy. All patients received oral etoposide (VP-16), 50 mg Bid, 30 minutes before TRT beginning day 1 for 10 days, repeated on day 29, and cisplatin 50 mg/m(2) intravenously on days 1, 8, 29, and 36. Patients in the study group received amifostine, 500 mg intravenously, twice weekly before chemoradiation (arm 1); patients in the control group received chemoradiation without amifostine (arm 2). Patient and tumor characteristics were distributed equally in both groups. Of the 60 patients enrolled, 53 were evaluable (27 in arm 1, 26 in arm 2) with a median follow-up of 6 months. Median survival times were 26 months for arm 1 and 15 months for arm 2, not statistically significantly different. Morphine intake to reduce severe esophagitis was significantly lower in arm 1 (2 of 27, 7.4%) than arm 2 (8 of 26, 31%; P =.03). Acute pneumonitis was significantly lower in arm 1 (1 of 27, 3.7%) than in arm 2 (6 of 26, 23%; P =.037). Hypotension (20 mm Hg decrease from baseline blood pressure) was significantly more frequent in arm 1 (19 of 27, 70%) than arm 2 (1 of 26, 3.8%; P =.0001). Only 1 patient discontinued treatment because of hypotension. These preliminary results showed that amifostine significantly reduced acute severe esophagitis and pneumonitis. Further observation is required to assess long-term efficacy.

Adult↗
PubMed2001

Primary signet-ring cell carcinoma of lung: immunohistochemical study and comparison with non-pulmonary signet-ring cell carcinomas.

Signet-ring cell carcinoma (SRCC) of lung is a rare variant of pulmonary adenocarcinoma. In view of this rarity, the question of whether an SRCC is primary pulmonary or metastatic arises frequently because the majority of SRCCs seen in lung are metastatic tumors having arisen in stomach, colon, or breast. On routine histologic examination it is difficult to distinguish between pulmonary SRCC from SRCC metastasizing from other organs. Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor that is almost exclusively expressed in thyroid and pulmonary epithelial cells. TTF-1 expression has been demonstrated in various neoplasms of lung; however, the expression of TTF-1 in SRCCs has not been investigated so far. In the present study, using an immunoperoxidase staining procedure on paraffin sections, we investigated the expression of TTF-1, cytokeratin 7, cytokeratin 20, and villin (a specific marker expressed in tumors of the digestive tract, renal proximal tubules, and hepatic bile ducts) in 32 SRCCs from various organs (17 lung, 5 breast, 5 stomach, and 5 colon). Fourteen (82.4%) of 17 pulmonary SRCCs exhibited TTF-1 positivity, whereas none of the SRCCs of other organs were positive for TTF-1. A cytokeratin profile (CK7+/CK20-) was identified in 94.1% of pulmonary SRCC, and although it differed from the profile exhibited in colonic SRCCs (CK7-/CK20+), a similar profile was seen in breast SRCCs and some SRCCs arising in the stomach. Villin was identified in 29.4% of pulmonary SRCCs and 20% (one case) arising in the breast. Although the pattern of villin immunostaining exhibited by nondigestive tract SRCCs (cytoplasmic) differed from those of digestive tract SRCCs (membranous), distinguishing between the two groups based on their pattern of immunostaining alone would be difficult. The results of this study indicate that TTF-1 is expressed in a high percentage of pulmonary SRCCs and is very specific and that TTF-1 would be extremely valuable in distinguishing pulmonary SRCCs from those arising in other organs.

Biomarkers, Tumor↗
PubMed2000

Phenolic compounds from the leaves of Cornus controversa.

Two novel phenolic compounds from the leaves of Cornus controversa (Cornaceae) were characterized as (-)-2,3-digalloyl-4-(E)-caffeoyl-L-threonic acid and (-)-2-galloyl-4-(E)-caffeoyl-L-threonic acid, using spectroscopic methods.

Phenols↗
PubMed1999

Gender differences in p53 mutational status in small cell lung cancer.

Mutations in the p53 tumor suppressor gene have been demonstrated to be one of the most frequent genetic abnormalities in human cancers. Previous studies have shown that the frequency of p53 mutations is significantly higher in small cell lung cancer than in non-small cell lung cancer. However, this conclusion was based in large part on data derived from tumor cell lines and from studies with relatively small sample sizes and biased gender populations. To determine the mutational frequency in the p53 tumor suppressor gene and a potential difference in gender, we analyzed primary small cell lung cancer tumors from 65 patients (37 males and 28 females) for p53 mutations between exons 5 and 9. Mutations were found in 37 of 65 tumors (57%) within the region of p53 analyzed. Interestingly, none of the tumors from females contained more than one mutation, whereas four of the tumors from males contained more than one mutation. The most common mutation in this population was an adenosine-to-guanine transition (27%), followed by guanine-to-thymidine transversion (17%) and guanine-to-adenosine transition (12%). The gender difference in p53 mutational rate identified in this study suggests that a higher proportion of female tumors may develop through pathways not involving p53 mutations.

Adult↗
PubMed1996

Optimal delivery of perioperative chemotherapy: preliminary results of a randomized, prospective, comparative trial of preoperative and postoperative chemotherapy for invasive bladder carcinoma.

PURPOSE: We performed a planned interim analysis of a randomized trial comparing initial to postoperative chemotherapy for bladder cancer. The purpose of our analysis was to detect early evidence of survival differences, tolerance to therapy influenced by the sequence of treatment, predictive value of clinical state and influence of methotrexate, vinblastine, doxorubucin and cisplatin (M-VAC) on bladder resectability. MATERIALS AND METHODS: A total of 100 consecutive patients were randomized to receive 2 M-VAC courses before and 3 courses after surgery (group 1) or 5 adjuvant M-VAC courses following cystectomy (group 2). Survival, clinical response, clinical and pathological stage, and toxicity were evaluated in this second timed interim analysis. RESULTS: Of all patients 70% received at least 4 M-VAC courses. Overall survival at 31.7 months (range 1.8 to 87.7) was similar in groups 1 (60%) and 2 (63%), and independent of clinical stage. Preoperative clinical staging accurately identified patients at high risk for recurrence, while 37 of the 48 group 2 patients (77%) were considered at high risk by pathological staging (P3b, P4a, node-positive and unresectable disease). Comparison of pathological stage revealed that 14 of the 51 group 1 patients (28%) achieved stage P0 while only 1 of the 48 group 2 patients (2%) had P0 disease at surgery (p= 0.00043). Disease was unresectable in 3 group 1 (6%) and 8 group 2 patients (17%, p= 0.09). Tolerance to treatment was not significantly different in the 2 study arms. CONCLUSIONS: No survival advantage was noted between neoadjuvant and adjuvant M-VAC in our interim analysis. However, results suggest that M-VAC chemotherapy may be effective in increasing the resectability of localized bladder cancer and may contribute to organ preservation. Clinical stage was a reliable predictor of pathological findings at surgery. Future studies can use clinical staging to determine therapy before surgery for the select stages that we treated. Identification of the subset likely to achieve complete pathological remission will permit the selection of patients for organ preservation strategies.

Adult↗
PubMed1993

Collecting duct carcinoma of the kidney.

Collecting duct carcinoma (CDC) is a recently recognised histological variety of renal carcinoma (RC) considered to arise from the epithelium of the collecting ducts. Diagnosis of this entity depends on well defined gross and microscopic criteria and is supported by a characteristic immunostaining pattern. The clinical features of these patients, the natural course of the disease and its response to treatment have not been clearly established. Between 1980 and 1990 we treated 12 patients (median age 43 years, range 16-62) with collecting duct carcinoma of the kidney. In addition to being relatively young, each patient had a strong family history of associated malignancies. Survival was short (median 22 months) and 11 patients presented with locally advanced or metastatic disease.

Adolescent↗
PubMed1991

Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis.

Prognostic predictors for node-negative breast carcinoma have not been clearly established. Immunostaining with Ki-67 antibody was performed on frozen sections of histologically proved node-negative breast carcinomas from 42 patients to examine its prognostic value and its association with other clinicopathologic and biochemical parameters, i.e., patient age and tumor size, histologic type, nuclear grade, mitotic rate, presence of vascular or lymphatic invasion, DNA ploidy, percentage of cells in S-phase, estrogen content, and c-erbB-2 amplification. Thirty-seven of the 42 tumors showed immunoreactivity with Ki-67 antibody in 1% to 55% of the tumor cells. A strongly significant correlation was observed between Ki-67 staining percentage and, respectively, nuclear grade, age, and mitotic rate. Nuclear grade 1 (the most anaplastic) tumors showed a significantly higher median percentage of cells stained (median, 14; range, 3 to 40) compared with nuclear grade 3 tumors (median, 0.5; range, 0 to 8). Thirteen patients developed recurrence; six of them died of disease. On univariate analysis, both 5-year disease-free and overall survivals were strongly associated with percentage of cells stained with Ki-67 antibody. Our results suggest that Ki-67 immunostaining correlates well with nuclear grade and clinical outcome in node-negative breast carcinoma. Because of small sample size analyzed in this study we were unable to do multivariate analysis. Therefore, further studies with larger number of cases are needed to determine whether tumor proliferative activity determined by Ki-67 immunostaining is an independent prognostic parameter or it merely reflects histopathologic features such as nuclear grade or mitotic activity.

Adult↗
PubMed1991

Studies of desensitization and cross-desensitization to immunologic and nonimmunologic stimuli that evoke contraction and histamine release in superfused guinea pig trachea.

This study examined the possibility that there is cross-desensitization between immunologic and nonimmunologic stimuli that evoke contraction and histamine release (HR) in the isolated guinea pig trachea. Compound 48/80 and D-tubocurarine were found to cause homologous and heterologous desensitization for both contraction and HR from superfused trachea. Specific antigen challenge of trachea obtained from animals sensitized with either IgG1 (ovalbumin [OA]) or IgE (oxazalone-human serum albumin [OX-HSA]) also resulted in homologous desensitization for both contraction and HR. However, in experiments with animals sensitized with both IgG1 and IgE antibodies, prechallenge with OA resulted in cross-desensitization to OX-HSA, whereas the reverse sequence was ineffective in eliciting this phenomenon. This may be related to the type of desensitization produced by each antigen (specific versus nonspecific) or to heterogeneity of mast cells in the tissue. Prechallenge of the trachea with compound 48/80 or D-tubocurarine failed to alter subsequent effects of antigen after active sensitization with OA or passive sensitization with either IgG1 or IgE antibodies. Small but statistically significant decreases in tracheal responses to D-tubocurarine were observed after antigen prechallenge to active both IgG1 and IgE antibodies. This is the first study to demonstrate a cross-desensitization between compound 48/80 and D-tubocurarine and the first to examine cross-desensitization with IgG1 and IgE antibodies in the guinea pig trachea. The overall conclusion is that there is no major overlap in the desensitization mechanisms between immunologic and nonimmunologic stimuli in the guinea pig trachea.

Animals↗
PubMed1991

Experimental fusarial hyalohyphomycosis in a murine model.

The pathogenicity of two clinical strains of Fusarium solani was studied in normal and transiently neutropenic outbred CF1 and CD1 male mice. Three inocula (5 x 10(5), 1 x 10(6), and 5 x 10(6) spores/animal) were tested. Groups of 10 mice each were injected with a single intravenous dose of one inoculum. Mortality correlated with the dose of inoculum, as survival was significantly shorter in mice injected with 5 x 10(6) cfu/mouse than in mice that received 1 x 10(6) or 5 x 10(5) cfu/mouse (P less than .001). Necrotizing abscesses with acute branching septate hyphae, neutrophil and macrophage infiltration, and hemorrhage were observed. The median survival of neutropenic mice was shorter than that of normal mice (P less than .001). Neutropenic mice did not show evidence of an inflammatory cellular reaction and exhibited significantly higher numbers of fungi per gram of infected tissue (P less than .001). Intact host defenses in normal mice were able to confine the infection to the kidneys after initial dissemination. In contrast, disseminated infection persisted in most organs in immunosuppressed animals.

Animals↗
PubMed1990

Direct sequencing analysis of transmembrane region of human Neu gene by polymerase chain reaction.

The neu gene in rat neuro/glioblastoma was found to be activated by a single point mutation in the DNA sequence encoding the transmembrane region of the neu-encoded p185 protein. The human homologue of the rat neu gene, termed c-erbB-2 or HER-2, can also be activated in vitro by a similar mutation in the corresponding region. Although the human neu gene was shown to be amplified/overexpressed in a large portion of human breast and ovarian cancer, no reports indicate that the human neu gene is activated by a point mutation in human tumor. To study the possible point mutation of neu gene in human tumors, we characterized the genomic structure in the transmembrane region of human neu gene, which in turn allowed us to determine DNA sequence in this region directly following DNA amplification by polymerase chain reaction. We analyzed 7 tumor cell lines (2 breast cancer, 1 neuroblastoma, 1 rhabdomyosarcoma, and 3 glioma) and 11 tumor tissue samples (8 breast and 3 ovarian cancers). No mutation was found in the transmembrane region of human neu gene. Our results suggest that unlike the rat neuro/glioblastoma, the single point mutation in the transmembrane region of the human neu gene is a rare event in human tumors. In this study, we developed a technique for direct DNA sequencing of the transmembrane region of the human neu gene. This technique makes it possible to screen a large number of tumor samples.

Amino Acid Sequence↗
PubMed1990

Immunohistochemical analysis of P-glycoprotein expression correlated with chemotherapy resistance in locally advanced breast cancer.

We analyzed the expression of P-glycoprotein in samples from 48 patients with locally advanced breast cancer. Tumor samples from 40 patients were obtained at mastectomy, which was performed after three cycles of induction chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine, and prednisone. P-glycoprotein expression distributed focally was observed in 20 tumors by the immunoperoxidase method using the anti-p170-monoclonal antibody C219. The percentage of the tumor cell population expressing P-glycoprotein varied from less than 5% to greater than 30%; expression was observed significantly more often in tumors that showed less than partial response to the preoperative chemotherapy. Furthermore, P-glycoprotein was not expressed in eight tumor specimens obtained at the time of diagnosis, prior to chemotherapy, from patients who subsequently had pathologic complete responses. A comparative study of P-glycoprotein expression before and after chemotherapy and upon recurrence of tumor was done on a limited number of samples. No significant differences in P-glycoprotein expression were found. Therefore, it is possible that an intrinsic, rather than acquired, drug resistance may play a role in the failure of induction chemotherapy for locally advanced breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

SIS/PDGF-B expression in benign and malignant human breast lesions.

Northern blots with poly(A)-selected RNAs were prepared from four primary human breast carcinomas and hybridized with a SIS/PDGF-B gene probe. High expression of a normal-sized 3.7 kb SIS/PDGF-B transcript was observed in three samples. These three carcinomas were all T3 (greater than 5 cm) lesions and were histologically infiltrating ductal carcinomas accompanied by moderate to marked desmoplasia. Furthermore in situ hybridization with photobiotinylated probes was performed and demonstrated that the SIS/PDGF-B expression was localized within the epithelial cells of malignant as well as benign lesions. It is possible that SIS/PDGFB expression within the epithelial cell components of nonmalignant as well as malignant breast lesions may be in part responsible for the stromal reaction.

Blotting, Northern↗