Patients at high risk of recurrence or metastases following radical surgery for Stage 1B and 2A cervical carcinoma include those with pelvic node metastases, lymphatic or vascular space permeation in the cervix by tumour cells, large size of the primary tumour, involvement of the full thickness of the cervix and parametrial spread. We report the initial results of adjuvant chemotherapy using a combination of cisplatinum, bleomycin and vinblastine in 22 patients who had undergone Wertheim radical hysterectomy and were thought to be at high risk of developing recurrence. The mean duration of follow-up was 23 months. All are alive after follow-up ranging from 13 to 43 months. Three patients developed recurrences--one in the pelvis, another at the posterior aspect of the urethral meatus and the third developed pulmonary secondaries at 20 to 23 months after surgery. Toxicity from the chemotherapy was acceptable.
Twelve patients with advanced inoperable non-small cell lung cancer (NSCLC) were treated with mitomycin, vinblastine and cisplatin (MVP) combination chemotherapy. The overall response rate was 33% (4 partial responses and no complete response) with a median survival of seven months. One responder above subsequently achieved complete remission following successful resection of his tumour and is still alive 14 months after initial chemotherapy. Responses were observed in patients with good performance status and limited disease. Side-effects were generally well tolerated and manageable. MVP is an effective regimen and the low response rate achieved here as compared to other centres is also discussed.
Small cell lung cancer (SCLC) disseminates early and has poor prognosis. However, SCLC is highly chemosensitive, thus chemotherapy has been established as the primary mode of treatment. Seventeen patients (15 males and 2 females) with median age of 60 years (range 49 to 74 years) were treated with combination cyclophosphamide 750 mg/m2, adriamycin 40 mg/m2, vincristine 1.4 mg/m2 on day 1 and etoposide (VP 16) 75 mg/m2 on days 1 to 3 (CAVE). This combination was given in 6 courses at 3 weekly intervals. The response to the chemotherapy and the quality of life of patients was assessed at the third cycle and after the completion of therapy (sixth cycle). The overall response rate was 76.4%; 52.9% achieved complete response and 23.5% had partial response. The survival rate at 6 months was 70.8% and 4 patients (23.5%) were still alive after 1 year of chemotherapy. The median survival after therapy was 36 weeks. There was a 30% overall improvement in the Karnofsky performance score at the completion of chemotherapy. This study illustrated that the CAVE regimen is effective and beneficial in the majority of our patients with small cell lung cancer.
This trial was carried out in Hospital Kuala Lumpur. Fifty-two patients who were scheduled to receive their first or subsequent courses of cancer chemotherapy with single dose cisplatinum containing chemotherapy regimens were evaluated. Thirty-four patients were given ondansetron in one group while 18 in the other group received metoclopramide with dexamethasone. The response to treatment was categorised as complete (0 emetic episode), major (1 or 2 emetic episodes), minor (3 to 5 emetic episodes) or failure (> 5 emetic episodes or rescue medication). Among the 52 patients, a complete or major control (0 to 2 emetic episodes) was achieved in 23/34 patients (68%) from the ondansetron group and in 3/18 patients (17%) from the metoclopramide with dexamethasone group (p < 0.002) on day 1. Similarly, the control of nausea was greater in the ondansetron group compared with the metoclopramide with dexamethasone group (p < 0.0009) on day 1. Two patients were excluded (dropped out) after day one from each of the two study groups due to excessive vomiting subsequent to cisplatinum therapy. From days 2 to 6, there was a trend in favour of ondansetron. Both treatments were well tolerated. The results of this trial show that in the prophylaxis of nausea and vomiting induced by cisplatinum containing chemotherapy, the efficacy of ondansetron is superior to that of a standard anti-emetic combination, metoclopramide with dexamethasone.
We report five patients who presented with seminoma of an undescended testis to highlight the importance of dealing with adult cryptorchidism. On the basis of the literature review and our experience, we advocate orchidectomy for post-pubertal cryptorchid patients of any age because follow-up may be difficult, and treatment for the tumour may be unsuccessful.
From August 1999 to January 2001, twelve chemotherapy naive patients with locally advanced and metastatic non-small cell lung cancer (NSCLC) in our hospital received vinorelbine and cisplatin. Ten patients had stage IV disease while two had stage HI disease. Patients' performance status (PS) were as follows: four had PS 1, six had PS 2, and one each PS 3 and 4. A total of 46 cycles were given as scheduled. Only major haematological toxicities were noted; one patient each with Grade 3 anaemia, Grade 3 and Grade 4 leucopenia, two had Grade 3 neutropenia and 5 had Grade 4 neutropenia without associated mortality. Three patients had Grade 3 alopecia and one had Grade 3 phlebitis. After three cycles, three patients demonstrated partial response and two had stable disease. For the four patients who completed 6 cycles, two demonstrated stable disease and two partial response. Symptom improvement was reported in all but one patient. Performance status was better in four, stable in six but declined in two patients. In conclusion, in patients with locally advanced and metastatic NSCLC, vinorelbine/cisplatin is a well-tolerated and active regimen, offering symptom palliation and improved performance status in a significant proportion of patients. KEYWORDS; Vinorelbine, lung cancer, chemotherapy.
To assess the long-term survival of patients with nasopharyngeal carcinoma (NPC) who were treated with conventional radical radiotherapy (RT) followed by adjuvant chemotherapy.
We describe a patient with myasthenia gravis and thymoma who developed recurrent severe myasthenic crises associated with the use of combination chemotherapy.
An adult, female Malayan sun bear (Helarctos malayanus) was diagnosed with squamous cell carcinoma of the rostral mandible. Initial treatment included bilateral mandibulectomy rostral to the lingual frenulum followed by intra- and perilesional cisplatin injections. Recovery after the procedure was uneventful and the Malayan sun bear adapted well to a shortened mandible. Histopathology indicated incomplete surgical excision of the tumor; therefore, radiation therapy was instituted weekly for four treatments at 2 Gy in parallel opposed fields (total 4 Gy each treatment) with one additional cisplatin treatment. Two years after initial presentation, the animal showed no recurrence of neoplasia.
This study investigated whether the alpha(1)-adrenoceptor subtype(s) mediating the vasoconstrictor actions of the renal sympathetic nerves were altered in rats with cisplatin-induced renal failure. Male Wistar Kyoto rats were used and half received cisplatin (5 mg/kg i.p.) to induce renal failure and were taken for study 7 days later. The renal blood flow reductions caused by electrical renal nerve stimulation and close intra-renal administration of noradrenaline, phenylephrine and methoxamine were determined before and after amlodopine (AMP), 5-methylurapidil (MeU), chloroethylclonidine (CEC) or BMY 7378. Water intake and creatinine clearance were decreased (P<0.05) by 40-50% while fractional excretion of sodium was increased two-fold in the cisplatin treated rats. Mean arterial pressure was higher, 110+/-2 versus 102+/-3 mmHg and renal blood flow was lower, 10.7+/-0.9 versus 18.9+/-0.1 ml/min/kg in the renal failure rats (both P<0.05). AMP, MeU and BMY 7378 decreased (all P<0.05) the adrenergically induced renal vasoconstrictor responses in the renal failure groups by 30 to 50% and in normal rats by 20 to 40%. In the presence of CEC, renal nerve stimulation and noradrenaline and methoxamine induced renal vasoconstrictor responses were enhanced (all P<0.05) in the renal failure but not in the normal rats. These data showed that alpha(1A)- and alpha(1D)-adrenoceptors were the major subtypes in mediating adrenergically induced renal vasoconstriction but there was no substantial shift in subtype in renal failure. The contribution of alpha(1B)-adrenoceptor subtypes either pre- or post-synaptic appeared to be raised in the renal failure rats.
Well differentiated villoglandular adenocarcinoma of uterine cervix is a rare tumour which usually occurs in young women. It is considered to be an indolent tumour with favorable prognosis and most of them were treated by conservative procedures. We report a 35 year old lady who came with complaints of 3 months amenorrhoea and an episode of spontaneous bleeding. Urine pregnancy test was negative. Physical examination revealed a cervical polyp. Histopathological findings were consistent with villoglandular papillary adenocarcinoma associated with high grade cervical intraepithelial neoplasia (CIN-3). Left parametrial and left ureteral involvement, proved by biopsy, causing left hydroureteronephrosis was detected. The patient was thus found to be in an advanced stage, stage- III b (FIGO). The patient is currently undergoing radiotherapy. A review of literature showed that only occasional cases showing disease spread have been reported, suggesting caution in the management and regular follow up of the patient.
The pathogenesis of cisplatin-induced renal failure is related to reduced renal blood flow due to severe tubular damage and enhanced renovascular resistance. It is also known that alpha(1)-adrenoceptors, the major subtype of alpha-adrenoceptors in renal vasculature play the pivotal role in regulating renal hemodynamics. With this background, we have hypothesized that the altered renal hemodynamics and enhanced renovascular resistance in cisplatin-induced renal failure might be caused by the altered alpha-adrenergic responsiveness with a possible involvement of alpha(1)-adrenoceptors in the renal vasculature. In a unique experimental approach with anesthetized rats, this study has therefore examined if there is any shift in the renovascular responsiveness to renal nerve stimulation and a series of alpha-adrenergic agonists in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats with cisplatin-induced renal failure in comparison with their body weight-matched normal controls. Thirty-two male rats of both WKY (n=16) and SHR (n=16) origin with body weight 236+/-7.9 g received cisplatin (5mg/kg i.p.). The renal failure was confirmed in terms of significantly reduced renal blood flow, reduced creatinine clearance, increased fractional excretion of sodium, increased kidney index (all P<0.05) and tubular damage. After 7 days of cisplatin, the overnight fasted rats were anesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and renal vasoconstrictor experiments were done. The changes in the vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by electrical renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine and methoxamine. It was observed that in the cisplatin-treated renal failure WKY and SHR rats there were significant (all P<0.05) reductions in the renal blood flow along with significantly (P<0.05) higher renal adrenergic responsiveness as compared with their non-renal failure controls. The data showed that in the renal failure WKY and SHR rats, the altered renal hemodynamics might be caused by an augmented renal adrenergic responsiveness. The results obtained further led us to suggest that the augmented renal adrenergic responsiveness in the cisplatin-induced renal failure rats were possibly mediated by the alpha(1)-adrenoceptors.
The leaves of Nerium indicum Mill. have been utilized traditionally to cure cancer. By Bioassay (BST) guided isolation method, six compounds were isolated from the CHCl3 extract of the leaves. Selectivity of these compounds (in 0.6-12,500 ng/ml) was tested on various human cancer (MCF7, EVSA-T, T47D, H226, IGROV, A498, WIDR, M19, HeLa) and normal (Vero) cells in vitro. Doxorubicin and cysplatin were used as positive controls. The result indicated that NiO2D (5alpha-oleandrin) possessed the best cytotoxic effect on HeLa cells (IC50, 8.38 x10(-6) mM) and NiO2C (16, 17-dehidrodeasetil-5alpha-oleandrin) on A498 cells (IC50, 1.43 x 10(-6) mM). Those two compounds were not cytotoxic to normal cell.
Matched MeSH terms: Cisplatin/pharmacology; Cisplatin/therapeutic use
Recent in vitro and in vivo studies have demonstrated that zerumbone (ZER) possesses anticancer properties. The main objective of this study was to examine the effectiveness of the combination of ZER and cisplatin (CIS) to treat cervical intraepithelial neoplasia (CIN) in vivo. Microculture tetrazolium assay and immunohistochemistry of proliferating cellular nuclear antigen were used to study the antitumor effect of ZER. Prenatally exposed female BALB/c mice were used as a model. The progenies with CIN were injected peritoneally with isotonic sodium chloride solution (positive control), CIS, ZER, and a combination of both compounds. All treated and untreated mice were humanely killed, and serum and cervix were obtained for interleukin 6 analysis and histopathologic studies using hematoxylin and eosin staining, respectively. Zerumbone has revealed an antitumor effect on human cervical cancer cells and downregulates immunoexpression of proliferating cellular nuclear antigen (P < 0.05). In vivo study indicates that ZER at 16 mg/kg and CIS at 10 mg/kg have a regressing effect on CIN. The combination of ZER and CIS also showed similar effectiveness in regressing CIN. Our results indicate that the combination of ZER and CIS has modulated the serum level of interleukin 6 when compared with that in mice treated with isotonic sodium chloride solution (P < 0.05). The effectiveness of combining ZER and CIS could be further explored as a new therapeutic intervention of early precancerous stages of carcinogenesis before the invasive stage begins.
BACKGROUND: Renal sympathetic innervation plays an important role in the control of renal hemodynamics and may therefore contribute to the pathophysiology of many disease states affecting the kidney. Thus, the present study aimed to investigate the role of the renal sympathetic nervous system in the early deteriorations of renal hemodynamics and structure in rats with pathophysiological states of renal impairment.
METHODS: Anesthetized Sprague Dawley (SD) rats with cisplatin-induced acute renal failure (ARF) or streptozotocin (STZ)-induced diabetes mellitus (DM) were subjected to a renal hemodynamic study 7 days after cisplatin and STZ administration. During the acute study, renal nerves were electrically stimulated, and responses in renal blood flow (RBF) and renal vascular resistance (RVR) were recorded in the presence and absence of renal denervation. Post mortem kidney collection was performed for histopathological assessment.
RESULTS: In innervated ARF or DM rats, renal nerve stimulation produced significantly lower (all p<0.05, vs. innervated control) renal vasoconstrictor responses. These responses were markedly abolished when renal denervation was performed (all p<0.05); however, they appeared significantly higher compared with denervated controls (all p<0.05). Kidney injury was suppressed in denervated ARF, while, irrespective of renal denervation, renal specimens from DM rats were comparable to controls.
CONCLUSIONS: Renal sympathoexcitation is involved in the pathogenesis of the renal impairment accompanying ARF and DM, and may even precede the establishment of an observable renal injury. There is a possible enhancement in the renal sensitivity to intrarenal norepinephrine following renal denervation in ARF and DM rats.
Various strains of Bacillus thuringiensis (Bt) have been found to produce parasporal proteins that are cytotoxic to human cancer cells. This study aims to establish the binding affinity of purified Bt 18 toxin for CEM-SS (T lymphoblastic leukaemia cell line), to determine if competition exists between the toxin and commercial anticancer drugs for the binding site on CEM-SS and to localise the binding site of the toxin on CEM-SS.
Recent gene expression profiling studies have identified five breast cancer subtypes, of which the basal-like subtype is the most aggressive. Basal-like breast cancer poses serious clinical challenges as there are currently no targeted therapies available to treat it. Although there is increasing evidence that these tumors possess specific sensitivity to cisplatin, its success is often compromised due to its dose-limiting nephrotoxicity and the development of drug resistance. To overcome this limitation, our goal was to maximize the benefits associated with cisplatin therapy through drug combination strategies. Using a validated kinase inhibitor library, we showed that inhibition of the mTOR, TGFβRI, NFκB, PI3K/AKT, and MAPK pathways sensitized basal-like MDA-MB-468 cells to cisplatin treatment. Further analysis demonstrated that the combination of the mTOR inhibitor rapamycin and cisplatin generated significant drug synergism in basal-like MDA-MB-468, MDA-MB-231, and HCC1937 cells but not in luminal-like T47D or MCF-7 cells. We further showed that the synergistic effect of rapamycin plus cisplatin on basal-like breast cancer cells was mediated through the induction of p73. Depletion of endogenous p73 in basal-like cells abolished these synergistic effects. In conclusion, combination therapy with mTOR inhibitors and cisplatin may be a useful therapeutic strategy in the treatment of basal-like breast cancers.