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Biomedical subjects

M Martelli

Publications and source records attributed to M Martelli.

At least 55 records · Page 3Linked to original sources
PubMed1998

Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial.

PURPOSE: The purpose of this study was to investigate the prognostic value of time to relapse in 188 adult patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) included on the Parma trial at the time of their first relapse. PATIENTS AND METHODS: The median follow-up of these patients is 102 months after registration onto the Parma study. Time to relapse was calculated from initial diagnosis, and a cutoff of 12 months was used to separate 77 patients defined as early relapse from 111 patients defined as late relapse. RESULTS: Patients with early and late relapses had significantly different overall response rates to salvage therapy with two courses of dexamethasone, high-dose cytarabine, and cisplatin (DHAP; 40% v 69%; P=.00007) and different 8-year survival rates (13% v 29%; P=.00001). Features at relapse with a negative prognostic value in univariate analysis were higher than normal lactic dehydrogenase (LDH) levels, tumor size greater than 5 cm, Ann Arbor stages III to IV, and Karnofsky score less than 80%. Therefore, multivariate analyses were performed. Time to relapse (P=.001) and LDH levels at relapse (P=.003) had independent prognostic value, whereas tumor size did not reach statistical significance in the logistic model that predicted overall response after two courses of DHAP. The study of prognostic factors for overall survival (OS) and progression-free survival (PFS) confirmed the prognostic value of time to relapse (P < .0001 for OS and P=.005 for PFS) independent of response or treatment after two courses of DHAP. CONCLUSION: Time to relapse may be used to stratify patients at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma.

Adult↗
PubMed1998

[High prevalence of hepatitis C virus infection in patients with non-Hodgkin's lymphoma at the onset. Preliminary results of an Italian multicenter study].

143 patients with non-Hodgkin lymphoma (NHL) at the onset entered this perspective study on NHL-associated risk factors. They were 87 males and 56 females with a mean age of 52.3 years (range 14.6-82.3). An associated hepatitis C virus (HCV) infection was found in 16 of the 143 NHL cases (11.2%; 95% CI 6.5-17.5). They were 11 males and 5 females [mean age 59.9] year with disseminated (13/16) or localized NHL disease (3/16)]. The NHL histological subgroup was low grade (6/16), intermediate grade (2/16) or high grade (8/16). The cell origin was B in 15/16 cases and B cell-T cell rich in 1/16. The discovery of HCV infection was contemporary to lymphoma diagnosis in 6/16 cases but preceded the NHL onset in the other 10 patients. In these 10 patients the median time between HCV infection diagnosis and NHL onset was 3.6 years (range 1-14.5). These data confirm that in Italy the prevalence of HCV infection in patients with NHL (11.2%) is significantly higher than expected in the general population (1.3-3.2%). The finding that, in most cases, HCV infection was definitely antecedent to NHL onset, usually by years, adds evidence to the possible causative role of the HCV in lymphomagenesis.

Adolescent↗
PubMed1997

Langerhans' cell histiocytosis in adults: a clinical and therapeutic analysis of 11 patients from a single institution.

BACKGROUND: Langerhans' cell histiocytosis (LCH) is a rare disorder of uncertain etiology, characterized by a wide clinical spectrum and varied behavior. METHODS: This retrospective study analyzed 11 adult patients with a diagnosis of LCH observed at the study institution between April 1988 and March 1993. RESULTS: Based on the sites and extent of disease at diagnosis, patients were divided into four categories. Group A was comprised of four patients with unifocal bone disease who had surgical curettage. At last follow-up only 1 patient was in continuous complete response (CCR) at 29+ months. The other 3 patients recurred at 3, 12, and 30 months, respectively, after surgery and at last follow-up were found to be in CR at 16+, 48+, and 124+ months, respectively, after therapy with vinblastine (VBL) and high dose methylprednisolone (HDMP). Group B was comprised of three patients with multifocal bone disease. Two of these patients received VBL + HDMP; at last follow-up, 1 patient was in CCR 8 months after completion of therapy, and the other developed progressive disease 11 months later. The third patient was treated with interferon (IFN) and at last follow-up was in CCR at 35+ months. Group C was comprised of 2 patients with bone and visceral disease who were treated with etoposide (VP-16) + HDMP; at last follow-up, 1 patient was in CCR at 42+ months and the other patient, who had isolated vulvar recurrence 16 months later, was in CR with treatment with local IFN. Group D was comprised of two patients with lung and lymph node involvement, one of whom was treated with VP-16 + HDMP and the other with cyclophosphamide, doxorubicin, vincristine, and prednisone; at last follow-up, both were in CCR at 30+ and 71+ months, respectively. CONCLUSIONS: VBL + HDMP showed efficacy in patients with bone disease, in particular those treated for recurrent LCH after surgery. Therapy with VP-16 and HDMP was successfully employed in patients with visceral disease. IFN was effective both for localized disease and in patients with multiple bone lesions.

Adult↗
PubMed1997

Pathogenetic and clinical implications of Bcl-6 and Bcl-2 gene configuration in nodal diffuse large B-cell lymphomas.

Bcl-6 (LAZ-3) and Bcl-2 gene rearrangements have been respectively reported in 20-35 per cent and 10-25 per cent of diffuse large B-cell lymphomas (DLBCLs). Although these genetic lesions have been associated with different clinical outcomes (i.e., more favourable in Bcl-6 rearranged cases and poorer in Bcl-2 rearranged cases), their prognostic significance is still controversial. In the present study, we have investigated by Southern blot analysis the Bcl-6 and Bcl-2 gene configuration in a series of 80 lymph nodes involved by well-characterized DLBCLs, histologically defined according to the REAL and the updated Kiel classifications. The molecular findings have been correlated with the clinical features at presentation and with response to therapy. The majority of cases (57/80 = 71.2 per cent) had a centroblastic morphology. Bcl-6 rearrangements were detected in 23/80 cases (28.8 per cent), and were similarly associated with centroblastic (18/57 = 31.6 per cent) or immunoblastic (3/11 = 27.3 per cent) histotypes. In contrast, Bcl-2 was found to be rearranged in only three cases of centroblastic lymphoma (3.8 per cent). No significant differences were found between Bcl-6 rearranged and germline cases, as far as the clinical features at presentation are concerned. Forty-one patients, in whom the lymph node biopsy was performed at diagnosis, could be evaluated for response to treatment and clinical outcome. Most of these cases (30/41 = 73.2 per cent) were nodal DLBCL, without extranodal site involvement. Analysis of the clinical outcome showed no statistically significant differences between Bcl-6 rearranged and Bcl-6 germline cases (actuarial overall survival 50 per cent vs. 48 per cent, event-free survival 45 per cent vs. 46 per cent, at 4 years). These findings confirm that Bcl-6 rearrangements are the most frequent genetic lesion in DLBCL. The incidence of Bcl-2 involvement in our series is significantly lower than the figures reported in other studies, mainly from North American countries, probably reflecting heterogeneous patient selection and/or epidemiological variability. Finally, our results suggest that no relevant clinical differences are observed between Bcl-6 rearranged and Bcl-6 germline cases, when nodal DLBCLs are considered.

Adolescent↗
PubMed1997

Current guidelines for the management of aggressive non-Hodgkin's lymphoma.

The prognosis of aggressive non-Hodgkin's lymphoma (NHL) has improved greatly during recent years with the use of combination chemotherapy. Planning the treatment must take into consideration the patient's age, performance status, histological subtype and disease extent and severity. Recently, a 4-part International Prognostic Index (IPI), based on 5 prognostic factors, has permitted the allocation of patients with NHL in 2 well defined prognostic groups: good prognosis (low and low-intermediate risk) and poor prognosis (intermediate-high and high risk). Conventional chemotherapy with CHOP (a chemotherapeutic regimen consisting of a combination of cyclophosphamide, doxorubicin, vincristine and prednisone) or other equivalent third-generation regimens may be considered the standard treatment for the good prognosis group. In the poor prognosis group the probability of long term survival is less than 40% with conventional chemotherapy. Therefore, an early intensification with high dose therapy following peripheral stem cell transplantation (PSCT) should be considered in the setting of randomised trials. Localised stage disease, defined as stages I-IE and II-IIE without adverse prognostic factors, has a very good prognosis with a long term survival exceeding 80% using brief conventional chemotherapy regimens plus involved field radiotherapy. Refractory or relapsing patients after the drugs of first choice are given who subsequently respond to salvage chemotherapy should be enrolled for a course of high dose consolidation chemotherapy followed by PSCT. Elderly patients without severe organ dysfunction can take advantage from specifically devised chemotherapy regimens, with a response rate similar to that of younger patients. However, despite major advances in the treatment of aggressive NHL, additional clinical trials are required to enable the clinician to define the best therapeutic programmes to treat patients with this disorder.

Aged↗
PubMed1997

Multicentre experience with combined hyperthermia and radiation therapy in the treatment of superficially located non-Hodgkin's lymphomas.

The combination of Radiation Therapy (RT) and Hyperthermia (HT) has proved to be an effective treatment for a wide variety of superficially located recurrences of different tumors, particularly those arising in previously irradiated areas. Few studies on the use of HT in the management of lymphomatous diseases have so far obtained interesting results. Eight patients with Non Hodgkin Lymphomas (LNH) - 4 with cutaneous lymphomas and 4 with nodal recurrences after RT-Chemotherapy (CHT) treatment treated in three different Italian institutions with combined RT and HT are here reported. Rt dose ranged from 15 to 40 Gy with different fractionations, on the basis of previously received treatment. Hyperthermia was delivered using 432 or 915 MHz external microwave applicators, according to extension and depth of the lesions and available equipment. All patients tolerated well the HT treatment, and in all cases average intratumoral temperatures were >42 degrees, with 3 out of 10 treated sites achieving the goal of average temperatures >42.5%. One patient, with recurrent NHL, is disease-free after 24 months from completion of combined therapy. Our results seem to confirm previous experiences, suggesting a role of HT/RT not only for palliative purposes in cutaneous lymphomas, but also as an adjunct to radiotherapy alone in selected patients with superficially located recurrences.

Combined Modality Therapy↗
PubMed1996

Influence of age, lead axis, frequency of arrhythmic episodes, and atrial dimensions on P wave triggered SAECG in patients with lone paroxysmal atrial fibrillation.

Signal-averaged P wave of 42 patients with lone paroxysmal atrial fibrillation (PAF) and 29 normal subjects (N) were recorded, using three orthogonal leads and analyzed in the time and frequency (entire P wave or a 100-ms segment ranging from 75 ms before to 25 ms after the end of P wave) domains. PAFs were divided into a group of 12 having > or = 2 attacks a month (HF) and a group of 30 having < or = 2 attacks a year (LF). Statistically significant differences were absent with regard to ages of PAF and N; ages of HF, LF, and N at the time of signal-averaged ECG; ages of HF and LF at the time of the first arrhythmic episode; and elapsed times from the first episode. Length of P wave and some frequency-domain parameters were found to be significantly correlated with age. PAF showed a significantly longer duration of P wave in the frontal plane using the time-domain analysis. Frequency analysis was found to be useful in evaluating the influence of attack frequency. HF showed significantly higher values of some frequency-domain parameters than LF and N, while the three groups did not differ for time-domain analysis. P wave duration and frequency content of the three orthogonal leads proved to be significantly different in PAF and N. Right and left atrial echocardiographic dimensions proved to be higher (even if within normal limits) in HF than in LF and N. Results suggest that frequency analysis should be performed on the entire P wave.

Age Factors↗
PubMed1996

High-dose chemotherapy followed by autologous bone marrow transplantation versus dexamethasone, cisplatin, and cytarabine in aggressive non-Hodgkin's lymphoma with partial response to front-line chemotherapy: a prospective randomized italian multicenter study.

PURPOSE: To evaluate, in a prospective multicentric study, the efficacy of a conventional salvage chemotherapy (dexamethasone, cisplatin, and cytarabine [DHAP]) versus high-dose chemotherapy (carmustine, etoposide, cytarabine, and cyclophosphamide [BEAC]) followed by autologous bone marrow transplantation (ABMT) in patients with aggressive non-Hodgkin's lymphoma (NHL) in clinical partial response (PR) after two thirds of a conventional front-line therapy. PATIENTS AND METHODS: From August 1988 to August 1991, 286 patients with aggressive NHL were randomized in seven Italian institutions to receive fluorouracil, methotrexate, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as front-line therapy. Of the 286 patients enrolled onto the trial, 77 (27%) were considered in PR after two thirds of the front-line therapy, and 49 of 77 (64%) were randomized: 27 to receive DHAP chemotherapy and 22 to receive BEAC followed by ABMT. RESULTS: The response after second-line treatment was as follows: in the DHAP group, four patients (15%) achieved a complete remission (CR), 12 (44%) remained in stable PR, and 11 (41%) showed progressive disease; in the ABMT group, three patients (14%) obtained a CR, 18 (82%) obtained a stable PR, and one (4%) progressed, with an overall response (CR + stable PR) of 59% and 96% (P < .001) in the DHAP and ABMT groups, respectively. The overall survival was 59% versus 73% and the progression-free survival (PFS) was 52% versus 73% in the DHAP and ABMT groups, respectively (P, not significant). The toxicity was mild, particularly in the ABMT group, and no treatment-related deaths occurred in either group. CONCLUSION: Because of the small number of patients randomized, we were unable to determine whether ABMT or a standard salvage regimen (DHAP) is superior for PR patients. However, we confirmed that myeloablative treatment is a safe and well-tolerated procedure in this category of patients and this may enable us to evaluate its role as part of a front-line treatment in poor-risk NHL patients.

Adolescent↗
PubMed1996

Anaplastic large-cell lymphoma: clinical and prognostic evaluation of 90 adult patients.

PURPOSE: During the last few years, the application of CD30 monoclonal antibodies has led to the identification of a new lymphoma entity, termed anaplastic large cell lymphoma (ALCL). This tumor includes four distinct histologic subtypes, among which the Hodgkin's-like/Hodgkin's-related one (ALCL-HL) shares morphologic and phenotypic features with Hodgkin's disease (HD). PATIENTS AND METHODS: From September 1988 to October 1993, 90 ALCL patients were treated with third-generation chemotherapy regimens (either vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate with leucovorin, and prednisone [F-MACHOP] or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) during the course of an Italian multicentric randomized trial on high-grade non-Hodgkin's lymphomas (HG-NHL). In particular, 47 patients had ALCL of the common type (ALCL-CT) and 43 ALCL-HL. Null phenotype was the most common (39.8%), while T-cell, B-cell, and hybrid forms accounted for 35.5%, 22.2%, and 2.5%, respectively. RESULTS: Complete remission (CR) was achieved in 66 of 90 (73.5%) patients (33 of 47 [70%] with ALCL-CT and 33 of 43 [77%] with ALCL-HL). The majority of the patients in CR (56.5%) were alive and well at a median follow-up time of 38 months; no significant differences were observed between the two histologic groups, with the rate of complete responders being 49% and 65% in ALCL-CT and ALCL-HL, respectively. The probability of relapse-free survival (RFS), projected at 63 months, was 67% for ALCL-CT and 82% for ALCL-HL. The risk of lower CR and RFS rates was associated with the presence of bulky disease, advanced stage, and B symptoms. CONCLUSION: The data of the present study confirm that ALCL responds to third-generation chemotherapy regimens similarly to other aggressive malignant lymphomas in terms of both CR and RFS rates.

Adolescent↗
PubMed1996

[Staphylococcus aureus resistant to methicillin. Survey of prevalence in Yvelines hospitals].

During 2 months (01.01.95-28.02.95), we noted for each Staphylococcus aureus (SA) isolates, identification and susceptibility methods, hospital size, medical speciality, source, penicillin (P) and methicillin (M) susceptibility. For each non repetitive methicillin resistant SA we noted phenotype of aminoglycoside resistance of SA to 6 antistaphylococci drugs. We isolated 399 SA, SAP sensitives 6.5%, methicillin resistant SA (MRSA) 31.8%. MRSA in acute care unit 28.4%, non acute care unit 61.7%, surgery 28.6%, medicine 36.5%, orthopedics 34.5%, pédiatrics 4%, ICU 38.8%, others 10.3%. MRSA from wound 28.2%, respiratory tract 38.3% blood 22.5%, urine 58.5%, others 25.8% - MRSA kanamycin 1.7%, kanamycin tobramycin 36.2%, kanamycin, tobramycin, gentamicin 56.9% - MRSA erythromycin 79.5%, pefloxacin 91.3%, rifampicin 53.5%, acide fusidique 8.7%, fosfomycine 18.9%, TMP SMZ 5.5%. The proportion MRSA is equivalent among medical specialities predominant in urine cultures and respiratory tract. It should be better to carry on the survey for more than two months in each hospital.

Aminoglycosides↗
PubMed1996

Effect of ursodeoxycholic acid on hypertransaminasaemia and bile acid composition in patients undergoing bone marrow transplantation--a double-blind randomized control study.

A double-blind randomized placebo controlled trial of ursodeoxycholic acid was performed in 31 patients undergoing T-cell depleted allogeneic or autologous bone marrow transplantation to determine the effectiveness of this hydrophilic bile acid in improving the increase in serum liver enzymes that generally accompanies this procedure. Neither group showed any significant difference in magnitude of the increases in serum transaminases and gamma-glutamyltranspeptidase following the conditioning regimen that included chemotherapy and total body irradiation. In the 6 months after transplantation, serum enzymes decreased in both groups, but were consistently higher in the placebo treated patients, indicating that ursodeoxycholic enhances normalization of liver. Faecal bile acid showed that following chemotherapy and irradiation in which intestinal bacteria are ablated, secondary bile acid formation was practically abolished and faeces contained mainly cholic and chenodeoxycholic acids. During bile acid treatment, ursodeoxycholic acid accounted for 31.3 +/- 10.9% of faecal bile acids compared with 4.0 +/- 2.1% in the basal period. Serum and urinary ursodeoxycholic acid concentrations (mean +/- SD, 13.3 +/- 6.9 mumol/L and 2.65 +/- 0.84 mumol/L, respectively) were significantly higher in patients receiving bile acid than in thos on placebo (mean +/- SD, 0.15 +/- 0.12 mumol/L and 0.29 +/- 0.35 mumol/L, respectively) thus confirming compliance.

Administration, Oral↗
PubMed1996

[Analysis of the validity of vaginal-cervical cytologic examination in 162 pre- and post-menopausal patients].

The authors examine 162 cervico-vaginal smears of women in peri-menopause presenting cellular alterations (ASCUS). These patients were treated with a local topic therapy as the persistence of these alterations in 23 cases (14.2%) second level analyses were performed: gynecological visit, colposcopy and biopsy. In addition to inflammatory aspects 2 in situ carcinomas and 2 moderate dysplasias were recorded. We believe therefore that cytology could be a valid aid also in pre-menopausal women in the cervico-vaginal pathology.

Age Factors↗
PubMed1995

MACOP-B vs F-MACHOP regimen in the treatment of high-grade non-Hodgkin's lymphomas.

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities. Two hundred-eighty-six patients included between 15 and 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucositis among patients treated with MACHOP-B than among those given F-MACHOP (11% vs 3.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma.

Until now, literature data support the fact that the CHOP regimen represents the standard first line treatment for patients with advanced intermediate-grade non-Hodgkin's lymphoma. Recently, idarubicin has been introduced in clinical trials because of its favourable preclinical profile: it is more active than daunorubicin and doxorubicin against a number of experimental tumour systems and is significantly less cardiotoxic in animal models. From March 1991 to June 1993, 115 previously untreated patients with stage II to IV intermediate-grade non-Hodgkin's lymphoma, according to the Kiel classification, were enrolled in a phase III comparative trial. The objectives of the study were to compare the efficacy and safety of using idarubicin instead of doxorubicin in the polychemotherapeutic regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and dexamethasone). Of the 115 patients registered for the trial, 103 were evaluable: 52 received CH (doxorubicin)OP and 51 received CI(Idarubicin)OP. Known prognostic factors were equally distributed among the two groups. There were no significant differences between the 2 groups in the rates of partial and complete response. The overall response rate was 87%, with complete response in 62%: 63% in the CHOP group, and 59% in the CIOP group. At 30 months (median 20 months), 86% of all CR patients were alive without disease in the CHOP group and 85% in the CIOP group. Patients treated with CHOP experienced severe alopecia more frequently (P = .004). Only three patients in the CIOP group showed cardiac adverse events (1 moderate and 2 mild), while in the CHOP group 4 mild, 2 moderate and 1 severe were recorded. LVEF monitoring was carried out in 31 patients of the CHOP group and in 27 of the CIOP group. A median drop of 8.3% of the LVEF was observed in patients treated with CHOP regimen as compared to 4.8% in patients with CIOP regimen (P = .0001). In this trial, the "idarubicin arm" (CIOP regimen) was found to have an equivalent therapeutic efficacy and, slightly, reduced clinical toxicity in comparison to the standard doxorubicin-containing CHOP regimen in patients with intermediate-grade non-Hodgkin's lymphoma.

Adult↗
PubMed1995

[Surgical therapy of locally advanced non-small cell lung carcinoma].

Experience during the past 10 years has shown up different opinions on the surgical treatment of patients with stage III non-small cell lung cancer. In the light of high resectability and survival rates (respectively 80.8% and 40% at 2 years in the experience of the Southwest Oncology Group) produced with neoadjuvant therapy (followed by surgery) it appears to be an appealing therapeutic option. Until recently, there have been no large prospective randomized phase III trials to answer the question of whether neoadjuvant therapy is superior to other treatment modalities (surgical resection alone; non-surgical treatment).

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Importance of matrix metalloproteinases in human trophoblast invasion.

Human cytotrophoblast cells are invasive by virtue of their ability to secrete metalloproteinases (MMP) capable of digesting the extracellular matrix of the endometrium. It is the aim of the present study to determine which of the known MMP is responsible for this invasive behavior and to see to what extent endometrial secretions can modulate this enzymatic activity. Under our experimental conditions, first-trimester cytotrophoblast cells invade matrigel; this invasive behavior is inhibited by phenanthroline (an inhibitor of MMP) and by a polyclonal antibody to the 92-kDa gelatinase but not to other MMP. Since cytotrophoblast cells cultured in vitro secrete the 92-kDa gelatinase, and since adhesion to a substrate increases their gelatinolytic activity, it is believed that cytotrophoblast cells invade their surrounding matrix by binding to it and by increasing their secretion of 92-kDa gelatinase which then digests the collagen type IV of their micro-environment. This process of invasion is controlled by secretions from decidual cells (but not from non-decidualized stromal cells) since conditioned medium from decidual cells inhibits the activity of the 92-kDa gelatinase released from cytotrophoblast cells.

Animals↗