Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mechlorethamine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed1993

C-MOPP/ABV yields good results in a public hospital population with Hodgkin disease in Brazil.

BACKGROUND: Over the last 15 years, a number of combination chemotherapy regimens have been reported to induce more than 80% complete remissions (CR) in patients with advanced Hodgkin disease (HD). Almost all such studies have been conducted in large institutions from North America and Europe. It remains to be proven, however, that those regimens are equally effective for the larger population of patients with HD who live in very different social conditions in third-world countries. METHODS: Fifty-nine patients with advanced-stage or early bulky HD were treated in two public hospitals with the C-MOPP/ABV hybrid program, in which cyclophosphamide was substituted for mechlorethamine. RESULTS: The median number of cycles administered was six, and the median follow-up was 32 months. Fifty patients (85%) reached a CR. The actuarial failure-free survival (FFS) rate was 69%, and the actuarial overall survival rate was 78% at 68 months. The only significant prognostic factor that predicted for improved FFS rate was the absence of B symptoms (P = 0.02). Overall survival was better for patients who reached a CR (P = 0.0003) and those with no systemic symptoms (P = 0.007). Toxic effects were moderate, with one treatment-related death and six episodes of serious infection. CONCLUSIONS: The target population consisted of lower-class Brazilians, many living in poor social conditions. Nevertheless, these results compare equitably with other results reported in the literature. C-MOPP/ABV is an adequate treatment for HD in third-world populations.

Adolescent↗
PubMed1993

Pediatric stage IV Hodgkin disease. Long-term survival.

BACKGROUND: The optimal treatment for Stage IV Hodgkin disease (HD) remains uncertain, particularly the role of radiation therapy (RT). METHODS: A retrospective review of 43 children, 18 years of age or younger, who were seen and treated for Stage IV HD between June 1970 and June 1988, was performed. All patients were treated with combination chemotherapy (CT), and 20 patients received RT after CT (combined-modality therapy, CMT). CT consisted of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) in 41 patients and both MOPP and doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine in two patients. RT was added for patients who had a partial response (PR) to CT (n = 11) and/or for initial bulky thoracic disease (n = 12). RESULTS: With a median follow-up of 83 months, the 7-year actuarial freedom from progression (FFP) and survival rates for all patients were 69% and 78%, respectively. For patients achieving a complete response (CR) to CT, the 7-year FFP rate was 73% and for patients with a PR it was 90% (P value not significant). The actuarial overall survival rates at 7 years were 88% for patients with CR versus 80% for patients with PR. In contrast, patients with either no response (one patient) or progressive disease (four patients) after CT had a significantly worse prognosis than patients with CR, with a 7-year actuarial survival rate of 40% (P = 0.006). FFP after CT alone was significantly more prevalent in patients with Stage IVA (11 of 13 patients) than in patients with Stage IVB disease (2 of 10 patients; P = 0.003). For these symptomatic patients, failures were almost exclusively (seven of eight patients) in sites of initial nodal disease. The addition of adjuvant RT improved the progression-free survival for patients with B symptoms: 2 of 13 patients had relapses after CMT versus 8 of 10 patients treated with CT alone (P = 0.003). CONCLUSIONS: This retrospective analysis of MOPP alone compared with MOPP plus RT showed a significant difference in FFP in patients with Stage IVB HD favoring CMT.

Adolescent↗
PubMed2001

Advanced Hodgkin disease with large mediastinal involvement can be treated with eight cycles of chemotherapy alone after a major response to six cycles of chemotherapy: a study of 82 patients from the Groupes d'Etudes des Lymphomes de l'Adulte H89 trial.

BACKGROUND: The prognostic impact of large mediastinal involvement (mediastinum/thorax [M/T] ratio > 0.33) in advanced Hodgkin disease (HD) and the optimal treatment with chemotherapy or combined treatment remains controversial. METHODS: Among 533 assessable patients with Ann Arbor Stage IIIB/IV HD included in the H89 trial, 82 had large mediastinal mass defined on chest X-ray. All patients received induction with six cycles of chemotherapy (mechlorethamine, vincristine, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine or doxorubicin, vinblastine, bleomycin, procarbazine, prednisone); then complete and good partial responders were randomized between two consolidation treatments: 2 cycles of the same chemotherapy or (sub)total lymph node irradiation. RESULTS: Among 82 patients with an M/T ratio greater than 0.33, 48 were very large (ratio > 0.45). A large mediastinal mass was associated with supradiaphragmatic disease, younger age, histologic nodular sclerosis, and different sex ratio compared with other H89 trial patients. Biologic parameters and prognostic factors were similar for both groups. Although the major response rate to induction chemotherapy (after 6 cycles) was lower for patients with large mediastinal mass (78% vs. 86%), the 5-year overall survival rate (80% vs. 79%) and event free survival rate (59% vs. 61%) were similar (P = 0.64 and 0.3, respectively). The outcome was the same for patients (74%) with a large mediastinal mass randomized to 1 of the 2 consolidation arms. Analysis of progression showed that 68% (21 of 31) of failures occurred early during treatment and involved the mediastinum in 86% of the cases. CONCLUSIONS: For patients with large mediastinal mass and advanced HD who achieved a major response of at least 75% after 6 cycles of chemotherapy, a consolidation radiation therapy can be replaced by 2 additional cycles of chemotherapy.

Adult↗
PubMed1989

Advanced Hodgkin disease (clinical stages IIIB and IV): low relapse rate after brief chemotherapy followed by high-dose total lymphoid irradiation.

From January 1980 to September 1986, 50 patients with Hodgkin disease, clinical stages (CS) IIIB (26 cases) and IVB (24 cases) were treated by three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, followed by high-dose (40 Gy) (sub)total lymphoid irradiation, including the spleen. Ten patients (2 CS IIIB, 8 CS IVB) were in failure, and seven (4 CS IIIB, 3 CS IVB) died during their first complete remission (2 from treatment-related complications, 1 from unknown cause, 4 from insufficient supportive care and/or a shortage of health supplies); three patients (CS IIIB) relapsed (2 alive in second complete remission, 1 deceased). After 7 years, actuarial survival and relapse-free duration were, respectively, 64% for the 50 patients and 89% for the 40 patients in complete remission. Unfavourable outcome was observed in patients with pelvic nodal involvement. The low relapse rate (none in CS IVB) was the most striking result after brief chemotherapy followed by total lymphoid irradiation.

Adolescent↗
PubMed2002

European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease.

BACKGROUND: Lymphocyte-predominant Hodgkin disease (LPHD) is rare and has a natural history different from that of classic Hodgkin disease. There is little information in the literature regarding the role of chemotherapy in patients with early-stage LPHD. The objective of this study was to examine recurrence free survival (RFS), overall survival (OS), and patterns of first recurrence in patients with LPHD who were treated with radiotherapy alone or with chemotherapy followed by radiotherapy. METHODS: From 1963 to 1996, 48 consecutive patients ages 16-49 years (median, 28 years) with Ann Arbor Stage I (n = 30 patients) or Stage II (n = 18 patients), very favorable (VF; n = 5 patients) or favorable (F; n = 43 patients) LPHD, according to the European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte (EORTC-GELA) criteria, received radiotherapy alone (n = 37 patients) or received chemotherapy followed by radiotherapy (n = 11 patients). The percentages of patients with VF disease (11% vs. 9% in the radiotherapy group vs. the chemotherapy plus radiotherapy group, respectively) or F disease (89% vs. 91%, respectively) within the two treatment groups were similar (P = 1.00). A median of three cycles of chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) was given initially to six patients and five patients, respectively. A median total radiotherapy dose of 40 grays (Gy) given in daily fractions of 2.0 Gy was delivered to both treatment groups. RESULTS: The median follow-up was 9.3 years, and 98% of patients were observed for > or = 3.0 years. RFS was similar for patients who were treated with radiotherapy alone and patients who were treated with chemotherapy followed by radiotherapy (10-year survival rates: 77% and 68%, respectively; P = 0.89). The OS rate also was similar for the two groups (10-year survival rates: 90% and 100%, respectively; P = 0.43). MOPP or NOVP chemotherapy did not reduce the risk of recurrence outside of the radiotherapy fields. CONCLUSIONS: MOPP or NOVP chemotherapy did not improve RFS or OS significantly in patients with VF or F LPHD, although the statistical power was limited. Ongoing clinical trials will help to clarify the role of a watch-and-wait strategy or systemic therapy, including anthracycline (epirubicin or doxorubicin), bleomycin, and vinblastine-based chemotherapy or antibody-based approaches, in the treatment of these patients.

Adolescent↗
PubMed2002

An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease.

BACKGROUND: The relative importance of prognostic factors in patients with early-stage Hodgkin disease remains controversial. The purpose of this study was to evaluate prognostic factors among patients who received chemotherapy before radiotherapy. METHODS: From 1987 to 1995, 217 consecutive patients ranging in age from 16 to 88 years (median, 28 years) with Ann Arbor Stage I (n = 55) or II (n = 162) Hodgkin disease underwent chemotherapy before radiotherapy at a single center. Most were treated on prospective studies. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone (NOVP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), cyclophosphamide, vinblastine, procarbazine, prednisone, doxorubicin, bleomycin, dacarbazine, and CCNU (CVPP/ABDIC), or other chemotherapeutic regimens were given to 160, 18, 15, 10, and 14 patients, respectively. The median radiotherapy dose was 40 Gy. Serum beta-2-microglobulin (beta-2M) levels ranged from 1.0 to 4.1 mg/L (median, 1.7 mg/L; upper limit of normal, 2.0 mg/L). We studied univariate and multivariate associations between survival and the following clinical features: serum beta-2M level above 1.25 times the upper limit of normal (n = 12), male gender (n = 113), hypoalbuminemia (n = 11), and bulky mediastinal disease (n = 94). RESULTS: Follow-up of surviving patients ranged from 0.9 to 13.4 years (median, 6.6 years) and 92% were observed for 3.0 or more years. Nineteen patients have died. Only elevation of the serum beta-2M level was an independent adverse prognostic factor for overall survival (P = 0.0009). CONCLUSIONS: The prognostic significance of a simple, widely available, and inexpensive blood test, beta-2M, has not been studied routinely in patients with Hodgkin disease and should be tested prospectively in large, cooperative group trials.

Adolescent↗
PubMed2004

Treatment of pediatric Hodgkin disease avoiding radiotherapy: excellent outcome with the Rotterdam-HD-84-protocol.

BACKGROUND: To reduce radiotherapy (XRT) induced toxicity of treatment of children with Hodgkin disease (HD) while maintaining a high cure rate, we introduced a risk-adapted protocol consisting of chemotherapy (CT) alone in 1984. PROCEDURE: The outcome of 46 children treated for HD from 1984 until 2000 according to the Rotterdam-HD-84-protocol was determined. Children with stage I-IIA disease (n = 23), were treated with six courses of epirubicin, bleomycin, vinblastine, and dacarbazine (EBVD). Children with stage IIB-IV disease (n = 23), were treated with three to five alternating cycles of EBVD and mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). RESULTS: At a median follow-up time of 8.6 years (range 2.6-18.3 years), the 10-year overall survival (OS) is 95% and the event-free survival (EFS) 91%. In 5/46 patients XRT was administered because of residual mediastinal mass. Four children relapsed, two of them died. Up until now only one patient developed hypothyroidism; no symptomatic cardiac or pulmonary dysfunction, no second malignancy has been diagnosed. CONCLUSIONS: Risk-adapted treatment consisting of CT alone is highly efficacious for children with HD and toxicity is low. XRT was administered in only a small minority of children with HD. CT should be the first choice for HD in children and XRT should preferably be used for those with refractory or histologically proven residual disease or relapse.

Adolescent↗
PubMed1979

Prolonged disease-free survival in MOPP-resistant Hodgkin's disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD).

Twenty-one patients with advanced Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, prednisone) were treated with ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). ABVD induced complete remission in 13 patients (62%) and partial remission in 2 (9.5%). In particular, complete response to ABVD was obtained in 7 of 13 patients who failed to respond to primary MOPP chemotherapy. After six cycles, no further therapy was given to patients in complete remission. At 36 months from starting ABVD, 69.7% of complete responders remain alive and free of disease, with a total survival of 73.4%. In contrast, none of the patients in whom partial response or nonresponse was observed was alive at 18 months. ABVD for six cycles was accompanied by mild and reversible toxicity. The results indicate that there is no cross-resistance between MOPP and ABVD. ABVD appears a simple effective, and tolerable multiple-drug chemotherapy for use in patients who are resistant to MOPP.

Adult↗
PubMed1992

Nitrogen mustard-DNA interaction in melphalan-resistant mammary carcinoma cells with elevated intracellular glutathione and glutathione-S-transferase activity.

We examined the relationship between intracellular levels of glutathione (GSH), glutathione-S-transferase (GST) activity, and the kinetics of DNA cross-links induced by the bifunctional alkylating drugs melphalan (MLN), chlorambucil (CLB), and mechlorethamine (HN2) in a rat mammary carcinoma cell line (WT) and in a subline selected in vitro for primary resistance to MLN (MLNr, 16-fold resistance). MLNr cells exhibit a 2-fold increase in intracellular GSH concentration and an approximately 5-fold increase in GST activity as compared with the parent cells. They are cross-resistant to a variety of drugs, including CLB (6-fold) and HN2 (14-fold). Treatment of WT cells with 30 microM MLN or CLB induced a significant accumulation of DNA-DNA cross-links for up to 8 h, which decreased over a 24-h period. In MLNr cells, no significant cross-link formation was induced by either MLN of CLB at any time between 0 and 24 h. Doses of up to 100 microM MLN failed to induce cross-links in MLNr cells. Formation of cross-links was observed immediately after treatment with HN2 in both cell lines and was followed by a subsequent decrease during a 24-h incubation in drug-free medium. At an equimolar concentration (30 microM), the numbers of HN2-induced cross-links were significantly lower in MLNr cells than in WT cells. However, treatment of MLNr cells with 60 microM HN2 resulted in cross-link levels similar to those obtained using 30 microM HN2 in WT cells. The 35% decrease in MLN accumulation observed in MLNr cells could not entirely explain the absence of cross-links, since thin-layer chromatographic analysis demonstrated that both cell lines accumulate a significant amount of MLN and metabolize it to the same extent. Significant amounts of MLN were also detected in nuclei isolated from WT and MLNr cells that had been treated with 30 microM [14C]-MLN. Intracellular depletion of GSH by a nontoxic concentration of L-buthionine-(S, R)-sulfoximine (BSO, 100 microM; about 70% GSH depletion) significantly sensitized MLNr cells to MLN and increased cross-link formation. A nontoxic concentration (50 microM) of ethacrynic acid (EA, an inhibitor of GST showing some specificity for Yc/Yp subunits) also sensitized MLNr cells to MLN and increased cross-link formation. Our data demonstrate that both EA and BSO are effective modulators of nitrogen mustard cytotoxicity in tumor cells resistant to alkylating drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1975

Irritancy of cyclophosphamide-derived aldehydes (acrolein, chloracetaldehyde) and their effect on lymphocyte distribution in vivo: protective effect of thiols and bisulphite ions1).

(1) A strategy is described for investigating agents such as N-acetylcysteine or penicillamine that might be used as adjuvant therapy with cyclophosphamide, to lessen the toxic side-effects of this latter drug caused by some of its metabolites. (2) The toxic effects of acrolein and chloracetaldehyde were determined by (a) their effects on lymphocyte circulation and (b) their oedemagenic activity in rats. (3) Stable thiols and bisulphite ions antagonised this aldehyde toxicity/irritancy; thiosulphate ions did not. (4) Thiosulphate and bisulphite ions antagonised the irritancy/toxicity of a mustard, mechlorethamine (HN-2). (5) The possible relationship of intrinsic irritancy to anti-inflammatory activity is discussed briefly.

Acetaldehyde↗
PubMed2002

Topical treatment with povidone iodine reduces nitrogen mustard-induced skin collagenolytic activity.

Recently we have shown that post-exposure treatment with povidone iodine (PI) protects against nitrogen and sulfur mustard-induced skin lesions. Since proteolytic activity is involved in skin damage caused by chemical irritants, we have studied the effect of iodine on mechlorethamine (HN2)-induced skin collagenolytic activities in the haired guinea pig model. The matrix metalloproteinase-9 (MMP-9) activity increased by 30, 46, 12 and 23% after 3, 24, 48 and 72 h of HN2 exposure, respectively, whereas the MMP-2 was elevated by 8, 65, 8 and 30%, respectively. Topical treatment with PI at 15 and 120 min after HN2 exposure decreased the MMP-9 activity by 67% and 60%, respectively, when skin was analyzed 3 h after exposure. The same trend was observed in the MMP-2 and MMP-1 activities after PI treatment. A stronger effect of PI treatment 15 min following exposure was observed in skin analyzed 24 h after exposure, i.e. a decrease of 83% and 88% in MMP-9 and MMP-2 activities, respectively. Similar findings were observed with an interval of 120 min between HN2 exposure and PI treatment. A much weaker effect was observed on MMP-1 activity. A similar trend of PI-induced reduction in the three types of collagenase activity was found in skin analyzed 48 and 72 h after exposure. Reduced collagenolytic activity may serve as one of the mechanisms by which iodine protects the skin against chemical insult.

Administration, Topical↗
PubMed1997

Protective effect of povidone-iodine ointment against skin lesions induced by sulphur and nitrogen mustards and by non-mustard vesicants.

Mustard gas (sulphur mustard, SM) is a powerful vesicant employed as a chemical weapon. The present study demonstrates the effect of povidone iodine (PI) ointment against skin toxicity caused by SM. Gross and histopathological examinations showed that application of PI up to 20 min following exposure to the vesicant resulted in marked skin protection. The shorter the interval between exposure and treatment the better was the protection achieved. PI was also effective against other mustards such as carboxybutyl chloroethyl sulphide (CBCS) and mechlorethamine. The fact that PI protected the skin against agents which cannot be oxidized such as iodoacetic acid, divinylsulphone and cantharidine showed that the antidotal effect of PI was unrelated to oxidation of the nitrogen and sulphur atoms of the mustards. PI ointment is proposed as an efficient protective agent against skin toxicity caused by mustards and other alkylators.

Animals↗
PubMed2001

Adult lymphoblastic lymphoma in Taiwan: an analysis of treatment results of 26 patients.

Lymphoblastic lymphoma (LBL) frequently affects young adults and usually presents with a mediastinal mass as well as bone marrow involvement. Although the frequency of LBL in the Far East is higher than that of Western countries, no reports regarding treatment of this disease have as yet been reported. We herein report our treatment experience and verify the efficacy of the Stanford/Northern California Oncology Group (NCOG) protocol for this disease and recommend treatment strategies for LBL patients. We retrospectively reviewed the medical records of adult LBL patients treated in our hospital from 1986 to 1996. Twenty-seven patients were diagnosed to have LBL. These patients' ages ranged from 17 to 73 years old with a median of 23. Nineteen patients had an initial stage IV disease. Of the 23 cases in which immunological studies were performed, 20 proved to be of T cell lineage, 1 of B cell type, and the other 2 lacked both T and B markers. Three major chemotherapeutic regimens including prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide-mechlorethamine, vincristine, procarbazine, prednisone (ProMACE-MOPP), cyclophosphamide, hydroxydaunomycin, vincristine, prednisone (CHOP), and the Stanford/NCOG protocol were used to treat 3, 6, and 15 patients, respectively. Two other patients were treated with two different chemotherapeutic regimens, respectively. One patient was excluded for analysis because of initial treatment by surgery. The complete response (CR) rates with ProMACE-MOPP, CHOP, and the Stanford/NCOG regimens were 0%, 17%, 80% and median overall survival 9, 8.5, and 15 months, respectively. Five patients with stage II-III diseases achieved long-term disease-free survival of 11-36 months with the Stanford/NCOG protocol with a median follow-up of 24 months. Four patients in late stage or relapse received allogeneic bone marrow transplantation (BMT). Two of them obtained long-term disease-free survival. Two other patients in CR were treated with high-dose chemotherapy (HDCT) supported with autologous BMT and peripheral blood stem cell transplantation (PBSCT), respectively. The patient receiving HDCT with autologous PBSCT died of LBL relapse 6 months after transplantation. The other patient undergoing HDCT with autologous BMT died of fulminant hepatitis 5.5 months after transplantation. The median overall survival of all these 26 patients was 12 months. B symptoms and treatment without the Stanford/NCOG protocol were found to have significantly negative impacts on both patients' overall and progression-free survivals. Our results suggest that the Stanford/NCOG protocol may be an effective chemotherapy for adult LBL and may provide long-term remission for patients in an early stage of disease. For those patients with LBL in an advanced stage or in relapse, HDCT with allogeneic or autologous BMT is probably the treatment of choice.

Adolescent↗
PubMed1999

Two different schedules for integrating filgrastim as adjuvant therapy in the treatment of patients with advanced stage Hodgkin's lymphoma receiving MOPP/ABV hybrid chemotherapy.

PURPOSE: Management of advanced-stage Hodgkin's disease with a MOPP/ABV hybrid regimen (mechlorethamine, vincristine, procarbazine, prednisone, Adriamycin, bleomycin and vinblastine) has yielded a high complete response rate (75-85%). However, myelosuppression can limit delivery of treatment. Filgrastim has been shown to reduce chemotherapy-related neutropenia and allow for on-time administration of planned doses of chemotherapeutic agents. The objective of this study was to find the best way to integrate filgrastim with the MOPP/ABV hybrid regimen. METHODS: Enrolled in this study were 24 patients (aged 18-52 years) with newly diagnosed, histologically documented Hodgkin's disease. In schedule I, patients received filgrastim (5 microg/kg s.c. daily) beginning on day 9, 24 h after administration of ABV. In schedule II, patients received filgrastim concomitantly with procarbazine on days 2-7 (starting 24 h after day-1 MOPP administration and stopping 24 h before ABV administration) as well as after ABV beginning on day 9. Filgrastim after ABV administration was administered until two consecutive ANC readings of 10 x 10(9)/l were achieved. RESULTS: All patients were able to complete all six cycles of therapy. There was a trend to fewer dose reductions in schedule II (0.76%) as compared to schedule I (4.2%) with a P-value of 0.077 (chi-squared test). Specifically, 11.6% of MOPP courses and 5.5% of ABV courses were dose-reduced in schedule I versus 1.7% and 1.4%, respectively, in schedule II. CONCLUSION: In conclusion, filgrastim was effective in supporting the delivery of the MOPP/ABV chemotherapy. Concomitant administration of filgrastim with procarbazine (days 2-7) appears to be safe and allows the maximum dose intensity of this therapy.

Adolescent↗
PubMed1997

Noninvasive procedure for in situ determination of skin surface aspartic proteinase activity in animals; implications for human skin.

The present study demonstrated a noninvasive procedure for in situ determination of stratum corneum aspartic proteinase in the living animal. A non-leaky well, containing [125I]S-carboxymethylated insulin B-chain (ICMI) as a substrate, was constructed on the shaved back of anesthetized guinea pigs and rats. The enzymatic activity was determined by measuring the radiolabeled trichloroacetic acid soluble material. We demonstrated pepstatin-sensitive proteinase activity bound to the skin surface indicating the involvement of aspartic proteinase(s) such as cathepsin D and/or E. Aged rats had about six fold lower activity than young animals. The proteinase activity was inhibited by the alkylating agent mechlorethamine and by the cosmetic propylene glycol. A similar procedure was carried out with intact human skin pieces obtained during plastic surgery. The activity was inhibited by antihuman cathepsin D antibodies. Cathepsin D was immunohistochemically localized in the corneal and granular layers of the epidermis. Skin surface aspartic proteinase/cathepsin D activity may serve as a marker for skin aging or for certain skin disorders leading to a new approach to their medical treatments.

Aging↗
PubMed2006

Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis.

In the present study, the toxicity of yperite, SM, and its structural analogue mechlorethamine, HN2, was investigated in a human bronchial epithelial cell line 16HBE. Cell detachment was initiated by caspase-2 activation, down-regulation of Bcl-2 and loss of mitochondrial membrane potential. Only in detached cells, mustards induced apoptosis associated with increase in p53 expression, Bax activation, decrease in Bcl-2 expression, opening of the mitochondrial permeability transition pore, release of cytochrome c, caspase-2, -3, -8, -9 and -13 activation and DNA fragmentation. Apoptosis, occurring only in detached cells, could be recognized as anoikis and the mitochondrion, involved both in cell detachment and subsequent cell death, appears to be a crucial checkpoint. Based on our understanding of the apoptotic pathway triggered by mustards, we demonstrated that inhibition of the mitochondrial pathway by ebselen, melatonin and cyclosporine A markedly prevented mustard-induced anoikis, pointing to these drugs as interesting candidates for the treatment of mustard-induced airway epithelial lesions.

Animals↗
PubMed1981

Long-term follow up of ovarian function in women treated with MOPP chemotherapy for Hodgkin's disease.

Twenty-seven women previously treated with MOPP (mechlorethamine, vincristine, procarbazine, prednisone) chemotherapy were evaluated to determine the status of ovarian function. All patients had completed therapy a median of nine years earlier and had a median age of 30 years at the time of evaluation. Persistent amenorrhea has occurred in 11 of 24 patients (46 percent) treated with MOPP alone or MOPP plus radiation excluding the pelvis. Of patients with amenorrhea, 89 percent were older than age 25 at the time of treatment. In contrast, 80 percent of patients younger than age 25 at treatment continue to menstruate regularly. The time from diagnosis to amenorrhea was significantly shorter in the older patients (p = 0.001). Evaluation of serum gonadotropin and estradiol levels confirms ovarian failure as the cause of amenorrhea in all patients. Overall, these 27 patients have borne 13 normal children subsequent to chemotherapy. This long-term follow-up study demonstrates that chemotherapy-induced ovarian failure is age-related, that ovarian failure is often gradual in onset following the completion of chemotherapy and that, to date, the children born of women treated with this chemotherapy regimen appear to be entirely normal.

Adolescent↗
PubMed1987

Salvage therapy of advanced Hodgkin's disease. Critical appraisal of curative potential.

The therapeutic outcome in patients with advanced Hodgkin's disease has improved considerably since the advent of MOPP chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone) and MOPP-like regimens. Still, failure will eventually occur in approximately 50 percent of these patients. The optimal approach to treating these patients is not well established. Currently, the six major salvage approaches available are: (1) chemotherapy reinduction with the same initial regimen: (2) chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine); (3) non-ABVD second-line regimens; (4) third-line chemotherapy regimens; (5) wide-field radiation therapy alone or combined with second-line chemotherapy; and (6) autologous and allogeneic bone marrow transplantation. This review provides a critical evaluation of the curative potential of each therapeutic modality and outlines recommendations for the best current therapeutic approach and for future clinical study.

Antineoplastic Combined Chemotherapy Protocols↗