Search PubMed⌕ Search

Biomedical subjects

V V Baker

Publications and source records attributed to V V Baker.

At least 37 records · Page 2Linked to original sources
PubMed1994

Postoperative adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy in women with high-risk endometrial carcinoma.

Because extrapelvic failure is common in women with high-risk endometrial carcinoma, the curative impact of adjuvant irradiation is limited. To address the issue of systemic failure, we prospectively treated 62 at-risk patients with postoperative chemotherapy between October 1985 and April 1992. Patients were considered eligible if they had grade 2 disease with mid- or outer one-third myometrial invasion, grade 3 tumor with any myometrial invasion, completely resected extrauterine disease, or variant histology (clear cell, papillary serous). Adjuvant therapy consisted of intravenous cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) given every 4 weeks for six courses. Toxicity was moderate: 31 patients (50%) had grade 3/4 neutropenia; dose reductions were mandated in 39 cases. However, there were only four hospital admissions for toxicity during 366 treatment cycles. All but three patients completed planned treatment. Recurrences have been noted in 14 of 29 patients with extrauterine disease and in 8 of 33 without. Eighteen of the 22 recurrences (82%) were outside the pelvis. At this writing, 17 patients with recurrence were dead, and 4 are alive with disease. Median time to recurrence was 13 months. Observed progression-free intervals for those with and without extrauterine disease are 26 and 36+ months, respectively, over a median follow-up period of 37 months. Actuarial 3-year survivals for those with and without extrauterine spread were 46 and 82%, respectively. Although adjuvant PAC did not prevent distant failure in women with extrauterine disease, the survival rate was greater than that anticipated for patients with disease confined to the uterus. A randomized trial comparing adjuvant irradiation to PAC is warranted in this subset.

Adult↗
PubMed1994

Oncogene expression in cervical cancer.

Significant advances have been made toward the understanding of the initiation and progression of cervical dysplasia and neoplasia at the molecular level. To date, this has not translated into improvements in diagnosis or treatment although it is a realistic expectation that this will occur. Significant variation in the proportion of tissue specimens that exhibit genetic alterations is striking. This may be attributed to different methods of analysis, different methods of tissue fixation, which influence antigen preservation, and the analysis of small numbers of samples per report, which introduces the possibility of sampling error. In spite of the variation among published reports, it is clear that several genetic alterations occur in preneoplastic and early-stage invasive cervical neoplasms. It remains to be determined which alterations of genetic structure or expression contribute to tumor initiation. The prognostic applicability of oncogene mutations is a particularly interesting area of investigation that is the closest to clinical application, although additional research involving larger numbers of patients is critical. The development of convenient methods of tissue fixation that preserve the myc oncoprotein, the synthesis of specific antibodies that provide consistent results, and the application of computer-assisted image analysis to quantitate results will be particularly important in this regard.

Female↗
PubMed1994

Improved accuracy in direct automated DNA sequencing of small PCR products by optimizing the template concentration.

Data are presented illustrating the optimum concentration range of reverse transcription PCR-generated products under 500 bp for accurate base calling with direct automated DNA sequencing. A 357-bp fragment of the human estrogen receptor, which includes the DNA binding domain of the protein, was used as a representative example of a gene fragment that can be rapidly amplified and sequenced. Using the Taq DNA polymerase dye terminator sequencing protocol and automated sequencing apparatus from Applied BioSystems, 0.1 to 1.0 pmol of PCR product in a 20-microL reaction volume provided > 97% accurate base detection. Concentrations greater or lower than this range increased the number of ambiguous bases due to alterations in the signal-to-noise ratios. This procedure has been successfully utilized with 140-440-bp PCR products within the optimum concentration range. These results show that low amounts of PCR products are necessary and sufficient for direct sequence analysis.

Base Sequence↗
PubMed1994

Molecular biology and genetics of epithelial ovarian cancer.

The majority of epithelial ovarian neoplasms occur in the absence of a familial or heritable component. Relatively little is known about the molecular genetic mechanisms that contribute to the development and progression of epithelial ovarian cancer. Although historically there have been difficulties encountered in basic science investigations, many key observations have been made during the past 5 years concerning the genetic alterations associated with this disease.

Female↗
PubMed1991

Detection of P-glycoprotein with JSB-1 monoclonal antibody in B-5 fixed and paraffin-embedded cell lines and tissues.

We analyzed the expression of P-glycoprotein (Pgp) by immunohistochemistry using JSB-1 monoclonal antibody (MAb) on paraffin-embedded sections of the multi-drug resistant (MDR) (CHrC5 and CEM-VLB), and sensitive (AuxB1 and CEM) cell lines, and also in normal kidney, colon, adrenal and in kidney and colon carcinomas. After comparing the sensitivity of three different immunohistochemical techniques the peroxidase-antiperoxidase method was found to be the best. We then tested six different fixation methods. The MDR cell lines and human tissues demonstrated the strongest staining with B-5 fixative. Both MDR cell lines, but not the tissues fixed in 1% paraformaldehyde and Zamboni's fixative demonstrated weak staining. No immuno- reactivity could be detected in MDR cell lines and tissues fixed in 10% buffered or nonbuffered formalin or by the AMeX method of tissue processing. The present study clearly shows that the type of fixative is critical for the preservation of Pgp epitope recognized by JSB-1 MAb, and that B-5 fixative is expected to be equally applicable for the detection of Pgp in normal and neoplastic tissues.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Autologous antibodies eluted from membrane fragments in human ovarian epithelial neoplastic effusions. III. Cytotoxic potential in vitro and characterization of antigen(s).

Cyst and ascites fluids from patients with ovarian epithelial neoplasms contain immunoglobulins with antitumor activity. Autologous antibodies bound to the cellular membrane fragments obtained from human ovarian neoplastic effusions react with cell-surface antigens on different human ovarian cell lines, surgical specimens of human ovarian adenocarcinoma, and human ovarian tumors grown in athymic Balb/c mice. The antibodies do not react with tissue preparations from normal human ovaries, other nonovarian normal or neoplastic tissues, and nonovarian human cell lines. These studies indicate that these antibodies are capable of complement-mediated lysis of human ovarian tumor cell lines in vitro. Preliminary characterization of the autologous ovarian tumor-associated antigen(s) indicates that it may be composed of three large-molecular-weight proteins of 182,000, 164,000, and 122,000 d.

Adenocarcinoma↗
PubMed1990

c-myc amplification in ovarian cancer.

The c-myc oncogene codes for a DNA binding protein that appears to play an important role in the regulation of cell growth. c-myc gene amplification has been documented to occur in both hematopoietic and solid neoplasms and often indicates more biologically aggressive tumors. Southern hybridization analysis was performed on high-molecular-weight DNA isolated from primary ovarian carcinomas. Major structural rearrangements of c-myc were not detected. Five of seventeen (29.4%) tumor samples demonstrated amplification of the myc oncogene. The 5 patients with ovarian carcinomas associated with c-myc amplification exhibited a median survival of 17 months. Of the 12 patients without evidence of tumor-associated c-myc amplification, 5 have exhibited disease-free survival for an average of 36.8 months and are currently alive. The remaining 7 patients, the majority of whom had advanced-stage, poorly differentiated lesions with a normal c-myc copy number, exhibited a median survival of 9 months. There was no apparent relationship between c-myc amplification, grade of tumor differentiation, and response to platinol-based chemotherapy. These data do not suggest a prognostic role for c-myc amplification in primary ovarian cancer. However, c-myc amplification is a common finding in advanced-stage ovarian cancer.

Adult↗
PubMed1990

Oncogene alterations in endometrial carcinoma.

The neu oncogene codes for a cell surface protein that has a high degree of homology with the epidermal growth factor receptor. Amplification of this oncogene in breast carcinoma and ovarian carcinoma is correlated with a poorer prognosis. The c-myc oncogene codes for a DNA binding protein and is believed to regulate cellular proliferation. Sixteen primary endometrial adenocarcinomas were analyzed for c-myc and c-neu amplification. Eleven of sixteen tumor samples exhibited amplification of the neu gene. Four of these eleven patients died of disease an average of 16 months after diagnosis. The five patients without tumor amplification of the c-neu gene have been followed an average of 31.2 months without evidence of recurrent disease. Ten of fifteen tumor samples exhibited amplification of the c-myc gene. Five of the ten patients died of disease an average of 13.4 months after diagnosis. The remaining five patients have been followed for an average of 31.2 months and are free of disease. Six of the sixteen tumor specimens exhibited amplification of the both c-neu and c-myc genes, and four of these patients died of recurrent disease. Amplification of the c-neu or c-myc oncogene correlated with advanced-stage disease and poorly differentiated lesions, suggesting that oncogene amplification may predict biologically aggressive adenocarcinomas of the endometrium.

Adenocarcinoma↗
PubMed1990

Pelvic exenteration with low rectal anastomosis: survival, complications, and prognostic factors.

Between July 1979 and January 1989 there were 31 patients who underwent pelvic exenteration with low rectal anastomosis (PE and LRA) at the University of Alabama at Birmingham (UAB). There were no operative deaths; however, 32% of the patients experienced significant postoperative morbidity. Survival (Kaplan-Meier) at 1 year is 86%. Overall survival is 68% with follow-up ranging from 10 months to greater than 9 years. For those patients with disease confined to the cervix and/or vagina (n = 18) the survival is 89% while it is 38% for patients with spread to the bladder, rectum, or parametrium (n = 13). Survival was not influenced by tumor differentiation, time from irradiation to exenteration, or initial stage. Complete healing of the LRA was achieved in 16 patients (52%). However, in the subset of patients with an omental wrap (n = 13) the complete healing rate is 85%. Protective colostomies were utilized in 12 patients; however, this was not shown to improve the healing rate of the LRA. This group of patients is compared to similar patients who had anterior pelvic exenteration at UAB for morbidity and survival. LRA at the time of pelvic exenteration for recurrent cervical cancer is associated with acceptable morbidity and survival and should be attempted in those patients who are appropriate candidates.

Adult↗
PubMed1990

Echinomycin (NSC 526417) in advanced ovarian cancer. A phase II trial of the Gynecologic Oncology Group.

Twenty-two patients with recurrent carcinoma of the ovary progressive after initial chemotherapy (21 with cisplatin-based treatment) were entered on a phase II trial utilizing Echinomycin at a dosage of 1,500 micrograms/m2 every 4 weeks. There were two complete responders and no partial responders (9% response, 95% confidence intervals for complete and partial responses of 1-29%). Major toxicity was modest and consisted mainly of nausea and vomiting. Echinomycin displays minimal activity as salvage therapy in women with advanced ovarian cancer at this dose and schedule.

Adult↗
PubMed1989

Factors affecting the response of recurrent squamous cell carcinoma of the cervix to cisplatin.

From June 1977 to June 1987 74 patients were treated with cisplatin for recurrent squamous cell carcinoma of the cervix as the primary chemotherapeutic agent. Sixty-eight patients were evaluable for response or survival. Patients with disease confined to the chest had a 53% complete response rate with an overall response rate of 73%. Patients with localized pelvic recurrences or persistence demonstrated no complete responses and a 21% overall response rate. Isolated chest metastases are more likely to respond to cisplatin than pelvic recurrences (P = 0.0007); however, location of recurrence did not significantly alter survival (mean 22.7 months versus 14.1 months; P = 0.24.). Concomitant disease in other locations reduced the likelihood of response in the chest (P less than 0.05) by virtue of lack of response in those other sites. Lesion size, clinical stage, patient age, and duration from primary treatment to recurrence were not of significance with regard to response or survival. When evaluating response to chemotherapy in recurrent cervical cancer, location of metastasis and effect on survival must be considered.

Adult↗
PubMed1989

A rapid DNA probe test for detecting human papilloma virus types 6/11 and 16 in biopsy specimens.

A simple, rapid and sensitive non-radioactive in situ hybridization assay for human papillomavirus (HPV) has been developed and used to detect HPV 6/11 and HPV16 DNA in ano-genital biopsy specimens. A comparative study to determine the sensitivity and the specificity of this assay relative to Southern blot hybridization assays was performed using one hundred biopsy specimens. The sensitivity of the in situ hybridization assay was 88% for HPV type 6/11 and 89% for HPV type 16. The specificity of the test was 99% for both virus types. In addition to its high sensitivity and specificity, this in situ hybridization assay for HPV uses a non-radioactive detection system. The assay is faster and easier to perform than the Southern blot method. Also, in situ hybridization assays permit the simultaneous evaluation of the histology, as well as the DNA content of biopsy tissues because they do not result in the destruction of tissue or cell morphology. This prototype HPV DNA assay was developed using DNA probes for HPV 6/11 and HPV 16 DNA in anogenital biopsy specimens. However, the protocol developed in these studies can easily be extended to include the use of probes for detecting other HPV types in a variety of tissues.

Anal Canal↗
PubMed1989

Clinical and histopathologic factors predicting recurrence and survival after pelvic exenteration for cancer of the cervix.

Between September 1969 and January 1, 1986, 143 pelvic exenterations for recurrent cervical cancer were performed by the gynecologic oncologists at the University of Alabama at Birmingham. Of this group, 78 patients underwent total pelvic exenteration, 63 patients had anterior exenteration, and two had posterior exenteration. The overall operative mortality rate was 6.3%, mostly associated with total pelvic exenteration. The 5-year survival rates were 50% overall, 63% with anterior exenteration and 42% with total exenteration. Univariate and multivariate analyses were performed to identify clinical and histopathologic factors predictive of prolonged survival. Using three clinical factors (duration from initial radiation therapy to exenteration, size of the central mass, and presence of preoperative sidewall fixation), low-, intermediate-, and high-risk groups were constructed; the 5-year survival rates for these groups were 82, 46, and 0%, respectively. Inclusion of one histopathologic factor (margin status of the surgical specimen) added to the ability to predict 2- and 5-year survival rates. The best candidates for cure by pelvic exenteration were those with recurrent small (less than 3 cm), mobile central masses who were a year or longer from the time of their previous radiation therapy. Attempts to resect bulky pelvic recurrences that impinge on the pelvic sidewall, especially in the case of persistent or early recurrent disease (within 6 months), or continuation of exenterative procedures in women known to have nodal metastases or extrapelvic spread, are generally futile. For those women falling between the two extremes, sound clinical and operative judgment is imperative in regard to selecting the treatment offering the best quality of life.

Adenocarcinoma↗
PubMed1988

Amplification of the c-myc proto-oncogene in cervical carcinoma.

Amplification without structural rearrangements of the c-myc proto-oncogene was found in 14 of 44 primary cervical neoplasms. There was no apparent correlation with stage of disease or degree of cellular differentiation. The prognostic significance of c-myc amplification cannot be determined from this study.

Adenocarcinoma↗
PubMed1988

Selective inhibition of c-myc expression by the ribonucleic acid synthesis inhibitor mithramycin.

Expression of the c-myc proto-oncogene has been shown to correlate with the rate of cellular proliferation and malignant transformation in a number of cell types. JEG-3 choriocarcinoma cells demonstrate c-myc transcript levels that are greater than those of nonmalignant trophoblastic tissue at any stage of gestation. Southern blot analysis documents c-myc gene amplification in JEG-3 cells, with a gene copy number of approximately 20. The methylation pattern and genomic structure of the amplified c-myc oncogene in JEG-3 choriocarcinoma cells are identical to those of normal placenta. Treatment of JEG-3 cells with mithramycin, a ribonucleic acid synthesis inhibitor, results in a dramatic decrease in c-myc expression relative to that of the c-Ha-Ras gene. The apparent selectivity of mithramycin for c-myc expression represents the only example, to date, of the selective pharmacologic modulation of oncogene expression.

Cell Line↗