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Biomedical subjects

F Major

Publications and source records attributed to F Major.

36 records · Page 2Linked to original sources
PubMed1993

Salvage intraperitoneal therapy of ovarian cancer employing cisplatin and etoposide: a Gynecologic Oncology Group study.

BACKGROUND: To further explore the potential of salvage intraperitoneal cisplatin-based therapy in patients with small-volume residual ovarian cancer a Phase II trial was conducted by the Gynecologic Oncology Group. METHODS: Ninety-two patients entered into this trial were treated with a regimen of cisplatin (100 mg/m2) and etoposide (200 mg/m2) delivered intraperitoneally every 4 weeks for a maximum of six cycles. RESULTS: Of the 84 patients evaluable for toxicity, grades 3-4 neutropenia, thrombocytopenia, neurotoxicity, and nephrotoxicity were observed in 25, 12, 6, and 9% of patients, respectively. A total of 41 patients were evaluable for response to the treatment program. Of the 25 evaluable patients with favorable pretreatment characteristics (prior response to systemic cisplatin or relapse > 6 months after completing initial chemotherapy), 10 (40%) achieved a surgically documented response (S-R), including 6 (24%) who achieved a surgically documented complete response (S-CR). Of the 16 patients with unfavorable pretreatment characteristics (less than a partial response to systemic cisplatin or a response of < 6 months duration) the S-R rate was only 12% (S-CR: 6%). CONCLUSIONS: In this large multi-institutional cooperative group study, we have confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer who have favorable pretreatment characteristics. The overall impact of these responses on disease-free and overall survival remains to be defined.

Adenocarcinoma↗
PubMed1991

The combination of symbolic and numerical computation for three-dimensional modeling of RNA.

Three-dimensional (3-D) structural models of RNA are essential for understanding of the cellular roles played by RNA. Such models have been obtained by a technique based on a constraint satisfaction algorithm that allows for the facile incorporation of secondary and other structural information. The program generates 3-D structures of RNA with atomic-level resolution that can be refined by numerical techniques such as energy minimization. The precision of this technique was evaluated by comparing predicted transfer RNA loop and RNA pseudoknot structures with known or consensus structures. The root-mean-square deviation (2.0 to 3.0 angstroms before minimization) between predicted and control structures reveal this system to be an effective method in modeling RNA.

Algorithms↗
PubMed1990

Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials.

About a third of patients with ovarian cancer present with localized disease; despite surgical resection, up to half the tumors recur. Since it has not been established whether adjuvant treatment can benefit such patients, we conducted two prospective, randomized national cooperative trials of adjuvant therapy in patients with localized ovarian carcinoma (International Federation of Gynecology and Obstetrics Stages Ia to IIc). All patients underwent surgical resection plus comprehensive staging and, 18 months later, surgical re-exploration. In the first trial, 81 patients with well-differentiated or moderately well differentiated cancers confined to the ovaries (Stages Iai and Ibi) were assigned to receive either no chemotherapy or melphalan (0.2 mg per kilogram of body weight per day for five days, repeated every four to six weeks for up to 12 cycles). After a median follow-up of more than six years, there were no significant differences between the patients given no chemotherapy and those treated with melphalan with respect to either five-year disease-free survival (91 vs. 98 percent; P = 0.41) or overall survival (94 vs. 98 percent; P = 0.43). In the second trial, 141 patients with poorly differentiated Stage I tumors or with cancer outside the ovaries but limited to the pelvis (Stage II) were randomly assigned to treatment with either melphalan (in the same regimen as above) or a single intraperitoneal dose of 32P (15 mCi) at the time of surgery. In this trial (median follow-up, greater than 6 years) the outcomes for the two treatment groups were similar with respect to five-year disease-free survival (80 percent in both groups) and overall survival (81 percent with melphalan vs. 78 percent with 32P; P = 0.48). We conclude that in patients with localized ovarian cancer, comprehensive staging at the time of surgical resection can serve to identify those patients (as defined by the first trial) who can be followed without adjuvant chemotherapy. The remaining patients with localized ovarian cancer should receive adjuvant therapy, and with adjuvant melphalan or intraperitoneal 32P should have a five-year disease-free survival of about 80 percent.

Adult↗
PubMed1990

Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.

There were 732 evaluable patients with primary, previously untreated, histologically confirmed stage I squamous carcinoma of the cervix with greater than or equal to 3-mm invasion. Of these, 645 had no gross disease beyond the cervix/uterus, had negative paraaortic lymph nodes, and had undergone a radical hysterectomy with pelvic lymphadenectomy. The 3-year disease-free interval (DFIs) for the 545 patients with negative pelvic nodes was 85.6%, and for the 100 with positive pelvic nodes, 74.4%. A large number of pelvic nodes involved with tumor was not correlated with a poorer prognosis; the DFIs were 72.1, 86.4, and 64.6% for one, two, and three or more positive pelvic nodes, respectively. DFI correlated strongly with depth of tumor invasion, both in absolute terms (mm) and infractional thirds. The DFI was 94.6% for less than or equal to 5 mm, 86.0% for 6-10 mm, 75.2% for 11-15 mm, 71.5% for 16-20 mm, and 59.5% greater than or equal to 21 mm. In fractional terms, the DFI was 94.1% for superficial third, 84.5% for middle third, and 73.6% for deep third invasion. With respect to clinical tumor size, the DFIs were 94.8, 88.1, and 67.6% for occult, less than or equal to 3 cm, and greater than 3 cm, respectively. The DFI was 77.0% for those with positive capillary-lymphatic spaces (CLS) and 88.9% for those with negative CLS. Tumor grade and parametrial status correlated with DFI. DFI was not significantly different for age, disease status of the surgical margins, tumor description (e.g., exophytic), quadrant involved with tumor, uterine extension, and keratinizing status of tumor cells. Clinical tumor size, CLS, and depth of tumor invasion were independent prognostic factors.

Carcinoma, Squamous Cell↗
PubMed1990

Pattern searching/alignment with RNA primary and secondary structures: an effective descriptor for tRNA.

A convenient pattern-matching program using primary and higher-order structural features has been developed based on a 'backtracking' algorithm. A second implementation of the algorithm uses descriptors of structural features (including primary sequences) to align a list of homologous or highly similar sequences. An application of the pattern matcher to the search for tRNA and group I intron structural motifs in sequence data banks is presented. The design of a highly discriminate tRNA motif, common to all cellular tRNAs and not found in a control sequence bank, was accomplished using the pattern matcher in conjunction with the alignment program.

Algorithms↗
PubMed1989

A prospective surgical pathological study of stage I squamous carcinoma of the cervix: a Gynecologic Oncology Group Study.

Thirty-three institutions collaborating in the Gynecologic Oncology Group gathered surgical and pathological data on 1125 patients with primary, previously untreated, histologically confirmed stage I cervical carcinoma with more than 3 mm of invasion who were selected to undergo radical hysterectomy and paraaortic and pelvic lymphadenectomy. Of the 940 eligible, evaluable patients, 732 had squamous carcinoma. Of the study group, 87 (12%) did not undergo radical hysterectomy because of gross disease beyond the uterus or microscopic aortic node involvement documented at exploratory laparotomy. Among the 645 patients undergoing pelvic and paraaortic lymphadenectomy and radical hysterectomy, five risk factors were significantly associated with microscopic pelvic lymph node metastasis: depth of invasion (P = 0.0001), parametrial involvement (P = 0.0001), capillary-lymphatic space invasion (P = 0.0001), tumor grade (P = 0.01), and gross versus occult primary tumor (P = 0.009). The factors identified as independent risk factors for pelvic lymph node metastasis by multivariate analysis were capillary-lymphatic space involvement (P less than 0.0001), depth of invasion (P less than 0.0001), parametrial involvement (P = 0.0005), and age (P = 0.02). The model was used to predict the chance of a patient having nodal metastasis for any combination of risk factors.

Adult↗
PubMed1988

A secondary and tertiary structure editor for nucleic acids.

A major difficulty in the evaluation of secondary and tertiary structures of nucleic acids is the lack of convenient methods for their construction and representation. As a first step in a study of the symbolic representation of biopolymers, we report the development of a structure editor written in Pascal, permitting model construction on the screen of a personal computer. The program calculates energies for helical regions, allows user-defined helices and displays the secondary structure of a nucleic acid based on a user-selected set of helices. Screen and printer outputs can be in the form of a backbone or the letters of the primary sequence. The molecule can then be displayed in a format which simulates its three-dimensional structure. Using appropriate glasses, the molecule can be viewed on the screen in three dimensions. Other options include the manipulation of helices and single-stranded regions which results in changes in the spatial relationship between different regions of the molecule. The editor requires an IBM or compatible PC, 640 kbyte memory and a medium or high resolution graphics card.

Algorithms↗
PubMed1988

FUS: a system to simulate conformational changes in biological macromolecules.

In order to study the dynamics of protein and nucleic acid conformations, a molecular folding-unfolding system (FUS written in Lisp) has been developed. Secondary structure features of protein and nucleic acids are graphically represented by cubes in a modified 'Blocks World' paradigm. Modeling of protein and nucleic acid unfolding (denaturation) and folding of their three-dimensional structure is possible by the use of high level 'block' operators which allow displacement of these structural features in space. Due to the flexible nature of this program, FUS is a useful tool for the rapid evaluation of user-defined rules governing conformational changes. The use of FUS to unfold three common proteins (prealbumin, flavodoxin and triose phosphate isomerase) and a tRNA is presented.

Computer Simulation↗
PubMed1987

Results of second-look laparotomy in patients with early-stage ovarian carcinoma.

One hundred twelve patients with early (FIGO stage I and II) ovarian carcinoma had a second-look laparotomy performed after comprehensive surgical staging and randomization into clinical protocols. Of the 95 patients who were asymptomatic before second-look laparotomy, only 5% had positive findings. In contrast, 53% of the 17 patients with findings that suggested recurrence or bowel obstruction had disease at second-look laparotomy. Overall, only 13% of the entire group of 112 patients had recurrent disease at second-look laparotomy. Asymptomatic patients with early ovarian carcinoma who have undergone careful initial surgical staging followed by appropriate adjuvant therapy can be spared a routine second-look operation.

Female↗
PubMed1985

A randomized clinical trial of adjuvant adriamycin in uterine sarcomas: a Gynecologic Oncology Group Study.

After hysterectomy, 156 evaluable patients with stage I (limited to the corpus) or stage II (limited to the corpus and cervix) uterine sarcomas were randomly assigned to adjuvant chemotherapy with Adriamycin (Adria Laboratories, Columbus, Ohio) for six months or to no further treatment. Pelvic irradiation (external or intracavitary) was optional before randomization. Of 75 patients receiving Adriamycin, 31 have suffered recurrences compared with 43 of 81 receiving no adjuvant chemotherapy. This difference is not statistically significant. Moreover, there is no difference in progression-free interval or survival. The optional radiotherapy did not influence the outcome although there was a suggestion that vaginal recurrence was decreased by pelvic radiotherapy. The recurrence rates in specific cell types (leiomyosarcoma, homologous mixed mesodermal sarcoma, or heterologous mixed mesodermal sarcoma) were not significantly different although the pattern of recurrence differed, with pulmonary metastases being more common in leiomyosarcoma and extrapulmonary recurrence being more common in mixed mesodermal sarcoma. The outcome with respect to chemotherapy was not altered even after adjusting for maldistribution of cases. Thus, we could not show a benefit for this dose schedule of Adriamycin as adjuvant treatment for uterine sarcomas.

Adolescent↗
PubMed1978

[Effects of a definite stress on the enzyme activities in blood plasma in mice (author's transl)].

The present study was designed to analyze the effects of a short term stress on the quantitative levels of alkaline phosphatase (AP), creatine phosphokinase (CK), aldolase (ALD), lactate dehydrogenase (LDH), and lactate dehydrogenase-1-isoenzyme (LDH 1) during 24 h after stress. For all the enzymes studied higher values for the activity were found due to stress in comparison to the activity level before the stress. The period during the 24 h after stress to reach maximum activity depends on the enzyme and in part on the sex of the animal.

Alkaline Phosphatase↗
PubMed1975

Study on sex-specific transferrin polymorphism and on the identification of transferrins by radioactive labelling.

Sex-specific differences with regard to the intensity of transferrin bands were observed in a noninbred adult mouse population after separation of the serum proteins by polyacrylamide gel electrophoresis. Amongst the female animals, an additional protein fraction was found just above the position of the transferrin bands. By means of a tracer method, using 59Fe-labelling, it could be shown that the additional fraction is not a part of the transferrin bands.

Age Factors↗