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M L Berman

Publications and source records attributed to M L Berman.

At least 19 recordsLinked to original sources
PubMed1992

Domain structure of human 72-kDa gelatinase/type IV collagenase. Characterization of proteolytic activity and identification of the tissue inhibitor of metalloproteinase-2 (TIMP-2) binding regions.

The 72-kDa gelatinase/type IV collagenase, a metalloproteinase thought to play a role in metastasis and in angiogenesis, forms a noncovalent stoichiometric complex with the tissue inhibitor of metalloproteinase-2 (TIMP-2), a potent inhibitor of enzyme activity. To define the regions of the 72-kDa gelatinase responsible for TIMP-2 binding, a series of NH2- and COOH-terminal deletions of the enzyme were constructed using the polymerase chain reaction technique. The full-length and the truncated enzymes were expressed in a recombinant vaccinia virus mammalian cell expression system (Vac/T7). Two truncated enzymes ending at residues 425 (delta 426-631) and 454 (delta 455-631) were purified. Like the full-length recombinant 72-kDa gelatinase, both COOH-terminally truncated enzymes were activated with organomercurial and digested gelatin and native collagen type IV. In contrast to the full-length enzyme, delta 426-631 and delta 455-631 enzymes were less sensitive to TIMP-2 inhibition requiring 10 mol of TIMP-2/mol of enzyme to achieve maximal inhibition of enzymatic activity. The activated but not the latent forms of the delta 426-631 and delta 455-631 proteins formed a complex with TIMP-2 only when excess molar concentrations of inhibitor were used. We also expressed the 205-amino acid COOH-terminal fragment, delta 1-426, and found that it binds TIMP-2. In addition, a truncated version of the 72-kDa gelatinase lacking the NH2-terminal 78 amino acids (delta 1-78) of the proenzyme retained the ability to bind TIMP-2. These studies demonstrate that 72-kDa gelatinases lacking the COOH-terminal domain retain full enzymatic activity but acquire a reduced sensitivity to TIMP-2 inhibition. These data suggest that both the active site and the COOH-terminal tail of the 72-kDa gelatinase independently and cooperatively participate in TIMP-2 binding.

Base Sequence↗
PubMed1992

Bulky stage IB cervical carcinoma managed by primary radical hysterectomy followed by tailored radiotherapy.

The management of bulky, stage IB cervical carcinoma remains controversial. The present study reports the outcome of 84 women treated by radical hysterectomy, in which the surgical specimen revealed a lesion measured to be 4 cm or greater in size following formalin fixation. Of the 84 women, 42 (50%) received postoperative radiotherapy based on additional surgical findings beyond tumor size suggesting a high risk for pelvic recurrence including lymph node metastasis, parametrial spread, and compromised margins. Despite the bulky nature of these lesions, major operative and early postoperative complication rates were low (6%). Delayed complications including fistulae and bowel obstructions occurred in only 2.4% of patients treated with surgery alone and in 14.2% of women treated with combined therapy. Corrected 5-year survival in this series was 70.4% (75.6% in the surgery only group and 65.0% in the surgery plus radiotherapy group). Recurrence and mortality rates were related to lesion size, with most recurrences and deaths occurring in women with lesions measuring 6 cm or greater. Comparison of these data utilizing primary radical hysterectomy followed by tailored radiotherapy with previously published data on similar groups of high-risk patients treated with either radiotherapy alone or with radiotherapy followed by simple hysterectomy suggests comparable survival and morbidity.

Adenocarcinoma↗
PubMed1992

Serum CA125 regression in epithelial ovarian cancer: correlation with reassessment findings and survival.

Findings at reassessment laparotomy and disease-free survival are reported for a group of patients with advanced-stage epithelial ovarian cancer who have had a complete clinical response to cytoreductive surgery and multiagent platinum-based chemotherapy. The predictive value of the number of chemotherapy cycles to achieve a serum CA125 of < 35 U/ml is compared to the predictive value of s, the rate of achieving a normal serum CA125. s is generated from an exponential regression model. This study suggests that s accurately predicts which patients have residual disease at reassessment laparotomy, who will be free of disease, and, of those in the latter group, who are at greatest risk to recur, as well as overall survival. If these observations are confirmed, physicians may base further therapeutic intervention on the basis of a calculated parameter following complete clinical response to first-line treatment rather than relying on findings at reassessment laparotomy.

Aged↗
PubMed1992

Analysis of fine-needle aspirates for HPV by PCR may be useful in diagnosis of metastatic gynecologic malignancies.

Human papillomavirus (HPV) DNA has been shown by molecular hybridization studies to persist in both recurrent and metastatic disease in tumors of the female genital tract. We report here the use of the polymerase chain reaction to identify HPV DNA in material from fine-needle aspirates (FNA) of recurrent or metastatic lesions to document the primary malignancy arising in the lower genital tract. Fine-needle aspirates of suspected recurrent or metastatic tumors were obtained from nine patients with carcinoma of the lower genital tract and five patients with malignancies that have not been associated with HPV. DNA was extracted from the FNA and tissue block, when available, and amplified with HPV 6, HPV 16, and HPV 18 specific primers. In eight of the nine tumors from the lower genital tract, HPV DNA was identified in both the primary and metastatic lesions. In every case the HPV genotype was identical. One cervical carcinoma and five non-HPV associated tumors were negative for papillomavirus DNA. This study demonstrates that molecular hybridization techniques can be useful in identifying the source of a metastasis and have the potential to diagnose the presence of metastatic disease by detecting HPV DNA even when the cytologic criteria are equivocal.

Biopsy, Needle↗
PubMed1992

Immunotherapy of ovarian cancer. II. In vitro generation and characterization of lymphokine-activated killer T cells from the peripheral blood of recurrent ovarian cancer patients.

We examined the in vitro sensitivity of continuous ovarian cancer cells to lymphokine-activated killer T cells (T-LAK) alone or in combination with cytokines. Lymphocyte viability in T-LAK cultures generated from normal donors and ovarian cancer patients declined in the first 2 to 4 days; however, the remaining cells in these cultures maintained a constant rate of proliferation for long periods in vitro. These cells became 90-95% CD3+ TCR+ -alpha/beta T-cells after 7-10 days in culture. The T-LAK cells from normal donors and cancer patients expressed an equal ability to induce lysis of a panel of human target cells (NK-sensitive K562, NK-insensitive RAJI, and two human ovarian tumor lines, SKOV-3 and OVCAR-3), demonstrating that they are nongenetically restricted killers. Preincubation of either the effector or target cells with tumor necrosis factor or interferon-gamma or addition of these cytokines directly to cytolytic assays did not alter the degree of cell lysis in vitro. This is a method for generating large numbers of autologous, cytolytically active T-LAK cells from the blood of ovarian cancer patients that could be employed in adoptive intraperitoneal immunotherapy.

Cell Division↗
PubMed1992

Reproductive, menstrual, and medical risk factors for endometrial cancer: results from a case-control study.

OBJECTIVE: Our objective was to evaluate the risk for endometrial cancer in relation to reproductive, menstrual, and medical factors. STUDY DESIGN: A case-control study of 405 endometrial cancer cases and 297 population controls in five areas of the United States enabled risk to be evaluated. RESULTS: A major risk factor was the absence of a prior pregnancy (relative risk 2.8, 95% confidence interval 1.7 to 4.6). The protective effect of pregnancy appeared to reflect the influence of term births, because spontaneous and induced abortions were unrelated to risk. Among nulliparous women infertility was a significant risk factor, with women having sought medical advice having nearly eight times the risk of those without difficulty conceiving. After adjustment for other reproductive characteristics, age at first birth and duration of breast-feeding were not related to risk. CONCLUSIONS: Elevated risks were found for subjects reporting early ages at menarche (relative risk 2.4 for ages < 12 vs > or = 15) and longer days of flow (relative risk 1.9 for > or = 7 vs < 4 days), but there was no relationship with late ages at natural menopause. Height was not associated with risk, but there was a significant relation to weight, with the risk for 200 versus < 125 pounds being 7.2 (95% confidence interval 3.9 to 13.3). After adjustment for weight and other factors, histories of hypertension and gallbladder disease were not significantly related to risk, but an effect of diabetes persisted (relative risk 2.0, 95% confidence interval 1.1 to 3.6). Hirsutism developing at older ages was also significantly related (relative risk 2.0, 95% confidence interval 1.2 to 3.4).

Adult↗
PubMed1992

Surgical treatment of unexpected invasive cervical cancer found at total hysterectomy.

OBJECTIVE: To determine the proper management of patients found to have invasive cancer of the cervix on pathologic examination of a uterus removed for benign indications. METHODS: We report 18 patients undergoing hysterectomy who were found to have cervical cancer with invasion deeper than 3 mm and/or lymph-vascular space involvement. None had gross residual tumor following simple hysterectomy. All patients underwent a second operation. Seventeen women underwent a radical parametrectomy, upper vaginectomy, and pelvic lymphadenectomy; one had pelvic and periaortic lymphadenectomy alone because of bilateral grossly positive obturator nodes. RESULTS: Median follow-up was 72 months. One of the 15 women without residual disease or nodal involvement at second operation had pelvic recurrence 66 months after therapy. Three patients with disease identified at radical surgery underwent tailored postoperative pelvic radiation, and two of these had pelvic recurrence. The overall actuarial 5-year survival for the 18 patients was 89%. Operative morbidity was comparable to that of patients undergoing primary radical hysterectomy. CONCLUSION: This study confirms that patients with unexpected invasive cervical cancer found at total hysterectomy can undergo radical re-operation with low morbidity and excellent cure rates.

Actuarial Analysis↗
PubMed1992

Effects of early postoperative chemotherapy on wound healing.

Wound complications were investigated in 100 patients undergoing chemotherapy for epithelial ovarian cancer and compared with wound complications in patients with other gynecologic malignancy who did not receive chemotherapy but were operated on by the same gynecologic oncologists. The incidence of wound complications in the chemotherapy-treated population was 11%. Complications developed with equal frequency regardless of when postoperative chemotherapy was initiated. Thus, chemotherapy did not increase the risk of wound complications despite efforts to begin chemotherapy as soon as possible after cytoreductive surgery. Low postoperative albumin levels (P less than .01), postoperative hemoglobin of 10 g/dL or less (P less than .02), advanced stage of disease (P less than .004), and electrocautery use (P less than .05) were all risk factors for development of wound complications, whereas the frequency of bowel resection and type of fascial or skin closure did not adversely influence the risk. Patients who received chemotherapy and developed wound breakdown actually healed faster than our control population. They healed at the same rate as did obstetric and gynecologic patients from the literature. Because delays in administering chemotherapy postoperatively have been associated with decreased survival, we recommend that chemotherapy for advanced-stage epithelial cancer not be delayed solely because of concern for wound healing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Inhibition of pseudocholinesterase activity protects from cocaine-induced cardiorespiratory toxicity in rats.

We studied the effect of inhibition of pseudocholinesterase by a specific pseudocholinesterase inhibitor, tetraisopropyl pyrophosphoramide (ISO-OMPA) on the cardiorespiratory toxicity of intravenously injected cocaine in rats. Group 1 rats received ISO-OMPA subcutaneously, whereas group 2 rats received saline placebo subcutaneously. Thirty minutes later, rats were anesthetized with 40 mg/kg of sodium pentobarbital intraperitoneally and were then given 10 mg/kg (least toxic dose) cocaine intravenously. Thirty minutes after the first injection of cocaine, about half of the rats that survived from each group were given 12 mg/kg cocaine (low toxic dose) intravenously, and the other half was given 13.5 mg/kg cocaine (high toxic dose) intravenously. Five minutes after each injection, rats were classified as either survivors or fatalities. In group 1 (ISO-OMPA treated), five of 29 (17%) rats that received 10 mg/kg cocaine, two of 11 (19%) that received 12 mg/kg cocaine, and three of 13 (24%) that received 13.5 mg/kg cocaine died of cardiorespiratory toxicity. In group 2 (saline treated), two of 29 (7%) that received 10 mg/kg cocaine, six of 12 (50%) that received 12 mg/kg cocaine, and 10 of 15 (67%) that received 13.5 mg/kg cocaine died of cardiorespiratory toxicity (p less than 0.03). Pseudocholinesterase activity (mean +/- SEM) of groups 1 and 2 were 0.6 +/- 0.2 and 7.3 +/- 0.7 units, respectively (p less than 0.01). Our results show that rats with lower pseudocholinesterase activity had lower fatality rates than rats with higher pseudocholinesterase activity.

Animals↗
PubMed1991

CA 125 regression: a model for epithelial ovarian cancer response.

The rate of decline of CA 125 in effectively treated epithelial ovarian cancer is described by the exponential regression curve CA 125 = EXP [i - s (days after surgery)]. In this equation i, the y-axis intercept, measures initial tumor burden whereas s, the slope of the regression curve, is determined by the extent of cytoreductive surgery and the subsequent response to chemotherapy. Departure from the regression curve uniformly results in progressive disease. In patients whose cancers had been completely removed, we calculated the mean half-life of CA 125 to be 10.4 days (range 4 to 21). In this case s = 0.0835 and characterizes the ideal regression rate. The model predicts that high-dose cisplatin chemotherapy (s = 0.0671) is more effective than low-dose cisplatin (s = 0.0380) (p less than 0.03) in eliminating residual cancer. Because s can be calculated within 2 to 3 months of treatment and then compared with s for the ideal regression curve and with the values of s reported for standard chemotherapy, evaluation of any new treatment protocol can be facilitated with this method.

Adult↗
PubMed1991

Clinical and histologic features of vulvar carcinomas analyzed for human papillomavirus status: evidence that squamous cell carcinoma of the vulva has more than one etiology.

The association between the human papillomavirus (HPV) and malignant neoplasms of the uterine cervix is well established; however, its role in the pathogenesis of vulvar cancer has not been well defined. This study correlates the clinical and histopathologic features of 21 invasive carcinomas of the vulva with the presence of HPV DNA as detected by Southern blot and polymerase chain reaction (PCR) analysis. By one or both techniques, HPV DNA was detected in 10 of the 21 tumors analyzed; all HPVs containing tumors hybridized with HPV-16 probes, although PCR also detected HPV-6 in two of the HPV-16-containing tumors. No HPV-18 DNA was detected in any tumor by PCR or Southern blot hybridization. Both the invasive cancer and the surrounding intraepithelial disease tended to display histopathologic features that usually could distinguish HPV-associated cancers from those without HPV DNA. The intraepithelial lesions associated with HPV-containing tumors were of the bowenoid type with koilocytosis, while tumors lacking HPV generally demonstrated a simplex type of intraepithelial lesion. Invasive tumors with no viral DNA were more frequently keratinizing than the HPV-containing cancers. Race, parity, hormonal therapy, and alcohol use did not affect the HPV status; however, HPV DNA was more prevalent in the tumors of younger women and in those with a history of tobacco use. Human papillomavirus status had no impact on the stage of disease or its prognosis. These findings identify two subsets of vulvar carcinoma cases based on HPV hybridization data and the histopathologic characteristics of the tumor.

Adult↗
PubMed1991

Radiation myelitis: a complication of concurrent cisplatin and 5-fluorouracil chemotherapy with extended field radiotherapy for carcinoma of the uterine cervix.

Radiation myelitis is a rare but serious complication of radiation therapy. The total dose of radiation to the spinal cord required to cause myelopathy is greater than 50 Gy when the treatment is administered in 25 or more fractions; however, recent evidence has suggested that the concurrent use of chemotherapy may decrease the tolerance of the spinal cord to radiation. This report describes a case of radiation myelitis in a patient after concomitant fluorouracil/cisplatin chemotherapy and extended field radiotherapy for stage IIA adenosquamous cell carcinoma of the uterine cervix metastatic to the para-aortic lymph nodes.

Adenocarcinoma↗
PubMed1991

Does intraperitoneal CA-125 reflect disease status?

The relationship of serum CA-125 to intraperitoneal (IP) CA-125 was studied in 45 patients with a variety of gynecologic diseases including ovarian carcinoma. In 43 of 45 patients the IP level exceeded the serum level of CA-125. Paracentesis may dramatically alter both levels, thus mimicking surgical debulking. All IP levels of CA-125 measured at second-look coeliotomy for the ovarian cancer patients were within the normal range of IP CA-125 measured at surgery for benign disease. Therefore, intraperitoneal CA-125 is less sensitive than serum CA-125 in predicting intraperitoneal disease status. Likewise it cannot be used to predict the subgroup of ovarian cancer patients with negative second-look coeliotomy who are destined to develop a recurrence of disease.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

Use of vaginal hysterectomy for the management of stage I endometrial cancer in the medically compromised patient.

Vaginal hysterectomy was performed on 31 patients with stage I endometrial cancer because of medical problems which placed them at high risk for morbidity and mortality from abdominal surgery. These risk factors included morbid obesity (87%), hypertension (58%), diabetes mellitus (35%), and cardiovascular diseases (26%). The perioperative morbidity was minimal, with only four patients (13%) experiencing complications requiring extended hospital stays and no deaths. Adjuvant radiotherapy was administered in 35% of patients with either deep myometrial invasion or unfavorable histology. The 3- and 5-year disease-free survival rates were 100 and 93%, respectively. The only cancer-related death occurred 4.5 years following surgery. Although the authors are not advocating vaginal hysterectomy as standard treatment of endometrial cancer, this approach provides an acceptable alternative to abdominal surgery in the medically compromised patient.

Adult↗
PubMed1991

Pulmonary artery catheter introducers: do the component parts affect flow rate?

Arrow sheath introducers are useful during massive transfusion as well as during catheter insertion. However, each component (sheath, side port, and obturator/catheter) probably progressively impedes maximum flow. This study quantitates these flow changes. Six configurations (C) were tested: (C1) sheath; (C2) sheath, side port; (C3) sheath, side port, obturator; (C4) C3 with 1.5-in obturator; (C5) C3 with 0.25-in obturator; (C6) no components. Flow was measured five times with each configuration and compared. Flows (mL/min) (mean +/- SE) were: (C1) 838.1 +/- 11.2, (C2) 283.4 +/- 9.2, (C3) 149.9 +/- 7.9, (C4) 176.0 +/- 14.0, (C5) 232.5 +/- 5.5, (C6) 1030.5 +/- 11.6. Flow decreased progressively with C2 and C3 (P less than 0.0001). C4 did not increase flow, but C5 did (P less than 0.0001). C5 flow was comparable to C2 but less than C1 (P less than 0.0001). C6 flow was larger than any other configuration (P less than 0.0001). Flow increases in C2 and C5 over C3 and C4 were modest (25%-50%) compared with C1 (250%). Therefore, we do not recommend removing or cutting the obturator to improve flow. During massive transfusion, we recommend removal of the side port until smaller flows suffice.

Catheterization↗
PubMed1991

Unusual metastases from a malignant melanoma. A case report.

An unusual case of malignant melanoma metastatic to the lung and to the ovaries occurred 9 and 11 years, respectively, after the initial, extragenital diagnosis. The primary lesion invaded to Clark's level IV with a thickness of greater than 4 mm, normally grave prognostic indicators. A metastatic lung nodule seen radiographically remained unchanged for two years before discovery of the intraperitoneal disease. The case illustrates the clinical variability and unpredictable biologic behavior of malignant melanoma.

Adult↗
PubMed1991

Early evaluation of the urinary tract following radical hysterectomy: structure and function relationships.

One hundred ten consecutive patients with invasive gynecologic cancers, treated by radical hysterectomy at The University of California, Irvine Medical Center, underwent early postoperative intravenous pyelogram (IVP). An abnormal early postoperative IVP did not predict subsequent urinary tract dysfunction (anatomical defect or disrupted voiding pattern) at 3 months, which occurred in 29% of the patients, nor did it detect any unsuspected fistulas or ureteral obstruction that persisted beyond the 3-month follow-up. Urinary tract dysfunction was not significantly associated with tumor volume, operative blood loss, or the type of radical hysterectomy performed. However, the inability to remove a suprapubic catheter before the 21st postoperative day was associated with a significant increase in urinary tract dysfunction at 3 months (P less than .03). We conclude that, in the absence of intraoperative urinary tract injury or clinical symptoms suggesting fistula or ureteral obstruction, the routine use of postoperative IVP should be abandoned.

Adult↗