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Objective To investigate the effect of insulin sensitizer rosiglitazone on blood METRNL levels. Methods After fed with high fat diet (HFD) for 3 months, obese mice were treated with rosiglitazone for 1 month. Glucose tolerance was tested with glucose tolerance test (GTT), and METRNL levels in blood were measured by ELISA. Real time fluorescence quantitative PCR was used to detect the expression of METRNL in various tissues such as muscle, liver, white fat, brown fat, brain, spleen and kidney, as well as the expression of mitochondrial proteins in brown adipose tissue. Results Glucose tolerance of animals fed a high-fat diet was improved in rosiglitazone group, and blood METRNL levels were also increased significantly in this group. Rosiglitazone treatment increased the expression of METRNL in brown fat and kidney tissue. There was no effect on METRNL expression in muscle, liver, white fat, brain and spleen. Rosiglitazone increased the expression of mitochondrial-associated proteins in brown adipose tissue. Conclusion The insulin sensitizer rosiglitazone might increase the serum METRNL level by increasing the METRNL expression in brown fat and kidney tissue, suggesting that METRNL may be involved in the therapeutic effect of rosiglitazone on diabetes.
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Protein tyrosine phosphatase (PTP) 1B is a potential therapeutic target for type 2 diabetes. Phosphotyrosine (pTyr) mimetics still dominate the currently available PTP1B inhibitors. The phenoxyacetic acid moiety was taken as a pTyr mimetic herein and phenoxyacetic acid-based compounds 2a-2g and 3a-3c were designed. Among them, compounds 2a-2g exhibited potent inhibition against PTP1B, and compound 2g showed an IC50 of 0.42 μmol·L-1 against PTP1B. Compound 2f exhibited pharmacological profiles similar to that of rosiglitazone, and could improve the insulin sensitivity and the serum total cholesterol level. The results suggest that PTP1B inhibitors might be effective in treating type 2 diabetes as well as associated metabolic syndromes.
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Radiotherapy still fails to achieve satisfactory efficacy in the treatment of malignant tumors, and applying radiotherapy sensitizers is an effective method to improve the efficacy of radiotherapy. Gold nanomaterials can effectively increase the sensitivity of tumor cells to radiotherapy due to their high atomic numbers. Gold nanoclusters have more excellent radiobiological and radiophysical properties due to their smaller size. This paper reviews the special radiobiological and radiophysical properties of gold nanoclusters and describes in detail their sensitizing effects in external radiation radiotherapy, radionuclide therapy, and X-ray induced photodynamic therapy.
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The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death (ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators. Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.
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OBJECTIVE: To investigate the asthma control status of occupational sensitizer-induced asthma(OSIA) and explore the influencing factors. METHODS: A total of 50 OSIA patients were selected as study subjects by judgment sampling method. Asthma Control Test(ACT) and Asthma Quality of Life Questionnaire were used to investigate the asthma control status and the quality of life of patients. The fractional exhaled nitric oxide(FeNO) level, pulmonary function, peripheral blood eosinophil ratio(EOS%)and serum total immunoglobulin E(IgE) level of the patients were measured. RESULTS: Among the 50 cases of OSIA patients, 27(54.0%) cases were well controlled, and 23(46.0%) cases were non-fully controlled. The patients with allergic rhinitis, with no inhaled corticosteroids treatment and with poor compliance were risk factors of the non-fully controlled OSIA(all P<0.05). The scores of ACT and the quality of life, and the percentage of the first second forced expiratory volume(FEV_1%) decreased(all P<0.05), while the level of FeNO increased(P<0.05) in the non-fully controlled group compare with the well-controlled group. There was no statistical significance in EOS% and serum total IgE level between the two groups(both P>0.05).CONCLUSION: Allergic rhinitis, lack of inhaled corticosteroids treatment and poor compliance are the influencing factors that affect the control of OSIA. The combinational scores of ACT and quality of life, FeNO, FEV_1% and other indicators can reflect the status of OSIA and assess the level of asthma control, and help guiding OSIA diagnosis and treatment plans.
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Recent studies indicate that insulin-sensitizing activity of TZDs occurs through the inhibition of PPARγ Ser273 phosphorylation mediated by cyclin-dependent kinase 5(Cdk5), which is resulted from the binding activity for PPARγ. While, the side effects of TZDs may be related to the agonistic potency for PPARγ. In this article, 15 target compounds were designed and synthesized based on the structure of PPAR γ partial agonist INT131, with the aim of maintaining the insulin-sensitizing activity and reducing the side effects of INT131. The structures of these compounds were confirmed by 1H NMR and ESI-MS, and their binding activities and agonistic potencies for PPARγ were measured. The binding activity of compound 15 is 88.47% of rosiglitazone, which is similar to INT131 (98.55%), but the agonistic potency of compound 15 is 1.41% of rosiglitazone, obviously lower than INT131 (15.18%).
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Aims: Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are beneficial in the management of diabetes by increasing insulin sensitivity and inhibiting hepatic gluconeogenesis. The aim of the present study was to investigate PPAR-γ agonist property of rutin, a flavonoid found in many plant species compared to thiazolidenediones (TZDs) using in silico approach. Methodology: Molecular docking of rutin on human PPAR-γ protein was determined by Vina plugin in PYMOL 1.3 and compared with thiazolidinediones, a known agonist of PPARγ. Results: Rutin acts as a potential agonist with binding energy of - 7.8 kcal/mol compared to thiazolidinediones with binding energy of - 4.1 kcal/mol. The molecular interaction of rutin was at residues of GLU 319, ILE 369, LEU 368, MET 362, PHE 321, PHE 310, LEU 497, ALA 320, LYS 289, ILE 354. Conclusion: We conclude that rutin is a better PPARγ agonist than TZDs confirming the capability of rutin for binding at the active site of the PPARγ.
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Photodynamic therapy (PDT) uses a photoactive dye (photosensitizer [PS])that activates by exposure to light of a specific wavelength in the presence of oxygen. The energy transfer from the activated PS to available oxygen leads to the formation of reactive oxygen species, such as singlet oxygen and free radicals. These chemical species are extremely reactive and can damage proteins, lipids, nucleic acids, and other components of the bacterial cell wall. Bacterial biofilms are widely implicated in their role in the causation of gingivitis and periodontitis. Prophylactic and therapeutic regimens for dental plaque related diseases include the usage of various chemotherapeutic agents. Since it is difficult to maintain therapeutic concentrations of these agents in the oral cavity and they run the risk of being rendered ineffective by bacterial resistance mechanisms, the need for an alternative antimicrobial approach in the treatment and prevention of dental plaque related diseases was felt. Many studies have reported the killing of bacteria via lethal photosensitization including both Gram-positive and Gram-negative bacteria. Photosensitization leads to bacterial elimination, with minimal chances of microbial resistance and with no adverse effects on host tissues and resident microflora. In dentistry, PDT has found use in the treatment of oral cancers, bacterial and fungal infections, and also in the detection of malignancies. PDT is free from genotoxic and mutagenic effects; another important factor for long-term safety. The ease of accessibility of the oral cavity to illumination makes it a suitable target for PDT.
Subject(s)
Humans , Laser Therapy/instrumentation , Laser Therapy/methods , Laser Therapy/therapeutic use , Laser Therapy/statistics & numerical data , Periodontitis/radiotherapy , Periodontitis/therapy , Photochemotherapy/instrumentation , Photochemotherapy/methods , Photochemotherapy/trends , Photochemotherapy/statistics & numerical dataABSTRACT
A prospective study was performed to evaluate the efficacy and safety of concurrent chemotherapy with single agent low dose Carboplatin and radiotherapy on survival, functional and quality of life outcomes in locally advanced head and neck cancer patients. Material and Methods : Sixty inoperable, previously untreated locally advanced head and neck cancer patients were planned to be treated with radical radiotherapy 66 Gy with concurrent single agent chemotherapy with low dose Carboplatin 150 mg IV weekly up to 6.3 weeks (Group A) and conventional radical radiotherapy alone (Group B). Results : After completion of therapy in Group A complete response was observed in 19/30 (63%) patient and in control group B in 10/30 (33%).Grade II mucosal toxicities were observed in 40% of cases and 33 % of cases in study and control group respectively. Conclusion : Concomitant single agent chemo radiotherapy with low dose Carboplatin could be a better choice in advanced stage of Head and Neck carcinoma in terms of survival, acceptable toxicities together with enhanced response and quality of life.
Subject(s)
Carboplatin/administration & dosage , Carboplatin/therapeutic use , Combined Modality Therapy , Female , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Humans , Male , Middle Aged , Radiotherapy , Radiotherapy DosageABSTRACT
Insulin resistance is a major risk factor for type 2 diabetes. AMP-activated protein kinase (AMPK) is a drug target in the improvement of insulin sensitivity. Several insulin-sensitizing medicines are able to activate AMPK through inhibition of mitochondrial functions. These drugs, such as metformin and STZ, inhibit ATP synthesis in mitochondria to raise AMP/ATP ratio in the process of AMPK activation. However, chemicals that activate AMPK directly or by activating its upstream kinases have not been approved for treatment of type 2 diabetes in humans. In an early study, we reported that berberine inhibited oxygen consumption in mitochondria, and increased AMP/ATP ratio in cells. The observation suggests an indirect mechanism for AMPK activation by berberine. Berberine stimulates glycolysis for ATP production that offsets the cell toxicity after mitochondria inhibition. The study suggests that mitochondrial inhibition is an approach for AMPK activation. In this review article, literature is critically reviewed to interpret the role of mitochondria function in the mechanism of insulin resistance, which supports that mitochondria inhibitors represent a new class of AMPK activator. The inhibitors are promising candidates for insulin sensitizers. This review provides a guideline in search for small molecule AMPK activators in the drug discovery for type 2 diabetes.
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Calcium sensitizer levosimendan has good clinical effect for heart failure patients with long-term administration of β-receptor blocker. The efficiency of levosimendan combined with digoxigenin is similar to that of levosimendan alone in treatment of heart failure. Compared with oral administration, the intravenous route s more effective. Administrating levosimendan for patients after heart surgery can shorten the recovery time and decrease the incidence of atrial fibrillation. Levosimendan also has cardioprotective effects on myocardium injured by ischemia and reperfusion. Piperphentonamine (PPTA) also has the effects of cardioprotection. Phase I clinical trial for PPTA has been finished in 127 healthy volunteers. The result shows PPTA has better tolerance and the human pharmacokinetic parameters in healthy subjects are in accordance with animal. The safety and efficacy of PPTA need o be defined by further clinical trials. This article summaries the clinical research advances related to calcium sensitizers levosimendan and piperphentonamine in recent years.
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In this study, we aim to compare the criteria for sensitizers among national organizations in various countries and international organizations, and to specify whether each Pollutant Release and Transfer Register (PRTR)-designated chemical substance is a sensitizer by each organization. The definition of sensitizing chemicals and the designation of respective sensitizers according to the PRTR law, Japan Society for Occupational Health (JSOH), American Conference of Governmental Industrial Hygienists (ACGIH), European Union (EU), and Deutsche Forschungsgemeinshaft (DFG) were studied. Of the 435 PRTR-designated chemical substances, 15 are listed as sensitizers according to the PRTR law, 16 as sensitizers of the airway and 21 as sensitizers of the skin by JSOH, 12 as sensitizers (no discrimination) by ACGIH, 19 (airway) and 85 (skin) by EU, and 15 (airway) and 43 (skin) by DFG. Only 9 substances were designated as sensitizers by all these organizations. The variation in the designation of sensitizers is accounted for by the differences in the classification criteria and grouping of chemical substances. JSOH limits the definition of sensitizers to substances that induce allergic reactions in humans and uses only human data. Other organizations utilize not only human evidence but also appropriate animal tests. In addition, EU designates an isocyanate as a sensitizer except those for which there is evidence showing that they do not cause respiratory sensitivity. The worldwide enforcement of the globally harmonized system (GHS) of classification and labeling of chemicals could promote not only the consistent designation of sensitizers among national and international organizations, but also the development of testing guidelines and classification criteria for mixtures.
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In this study, we aim to compare the criteria for sensitizers among national organizations in various countries and international organizations, and to specify whether each Pollutant Release and Transfer Register (PRTR)-designated chemical substance is a sensitizer by each organization. The definition of sensitizing chemicals and the designation of respective sensitizers according to the PRTR law, Japan Society for Occupational Health (JSOH), American Conference of Governmental Industrial Hygienists (ACGIH), European Union (EU), and Deutsche Forschungsgemeinshaft (DFG) were studied. Of the 435 PRTR-designated chemical substances, 15 are listed as sensitizers according to the PRTR law, 16 as sensitizers of the airway and 21 as sensitizers of the skin by JSOH, 12 as sensitizers (no discrimination) by ACGIH, 19 (airway) and 85 (skin) by EU, and 15 (airway) and 43 (skin) by DFG. Only 9 substances were designated as sensitizers by all these organizations. The variation in the designation of sensitizers is accounted for by the differences in the classification criteria and grouping of chemical substances. JSOH limits the definition of sensitizers to substances that induce allergic reactions in humans and uses only human data. Other organizations utilize not only human evidence but also appropriate animal tests. In addition, EU designates an isocyanate as a sensitizer except those for which there is evidence showing that they do not cause respiratory sensitivity. The worldwide enforcement of the globally harmonized system (GHS) of classification and labeling of chemicals could promote not only the consistent designation of sensitizers among national and international organizations, but also the development of testing guidelines and classification criteria for mixtures.
Subject(s)
Integumentary SystemABSTRACT
Polycysytic Ovary Syndrome (PCOS) is a common endocrine disorder characterized by chronic anovulation and hyperandrogenism. The etiology of PCOS is complex and incompletely understood. Accumulating data conclude that hyperinsulinemia and hyperandrogenemia may cause hormonal abnormalities that lead to disturbance of ovarian function. Although insulin resistance is not a part of the diagnostic criteria for PCOS, its importance in its pathogenesis can not be ignored. Excess insulin is capable of stimulating steroidogenesis and therefore excessive androgen production occurs from the theca cell system. Recently, the effects of insulin sensitizer in PCOS patients are being reported and they include the improvement of menstrual pattern, improvement in hyperandrogenism, increased response in ovulation induction and prevention of cardiovascular diseases. Understanding the relation of PCOS and insulin resistance will offer an improvement in treatment of PCOS in the future.
Subject(s)
Female , Humans , Anovulation , Cardiovascular Diseases , Hyperandrogenism , Hyperinsulinism , Insulin Resistance , Insulin , Ovary , Ovulation Induction , Polycystic Ovary Syndrome , Theca CellsABSTRACT
Several clinical studies suggest substantial limitations of currently available positive inotropic substances, including beta1-adrenoceptor agonists and phosphodiesterase III inhibitors. Levosimendan, a myofilament calcium sensitizer with inotropic effects, increases myocardial performance without substantial changes in oxygen consumption and with neutral effects on heart rhythm. In addition, levosimendan has vasodilatory effects that are achieved by stimulation of adenosine triphosphate-dependent potassium channels. This review article briefly discusses the pharmacology of levosimendan and evaluates current available evidence to assess the safety and efficacy of levosimendan.
Subject(s)
Adenosine , Calcium , Cyclic Nucleotide Phosphodiesterases, Type 3 , Heart , Myofibrils , Oxygen Consumption , Pharmacology , Potassium ChannelsABSTRACT
BACKGROUND: Insulin resistance is a central feature of polycystic ovary syndrome (PCOS), and hyperinsulinemia contributes to anovulation, oligo or amenorrhea, hyperandrogenism and infertility in women with PCOS. The use of insulin sensitizers, such as metformin or thiazolidinedione, in PCOS is becoming increasingly accepted. The purpose of our study was to evaluate the therapeutic effects of metformin and rosiglitazone on the metabolic and reproductive derangement, and find parameters predicting their therapeutic efficacy in Korean PCOS women. METHODS: Sixty-two women with PCOS were recruited. The baseline characteristics, including BMI, glucose tolerance test, lipid profiles, sex hormones and hyperinsulinemic euglycemic clamp test, were assessed. After the administration of the insulin sensitizer (metformin 1.5g/day or rosiglitazone 4mg/day) for 3 months, the insulin sensitivity was reassessed. A drug response was defined as menstrual restoration or pregnancy. RESULTS: Of the 62 women with PCOS, 36 gained restored regular menstruation, and a further 5 conceived (a drug response rate of 66.7%). There were no significant clinical differences between responders and nonresponders. Twelve weeks after taking the drugs, the insulin sensitivity was significantly improved (M-value 4.7+/-0.2 vs. 5.5+/-0.4mg/kg/min, P<0.05), and the free testosterone levels(72.5+/-39.9 vs. 45.8 +/-3.8pmol/L, P<0.05) were significantly decreased, without significant weight reduction. CONCLUSION: Metformin and rosiglitazone restored menstruation in 66.1% of women with PCOS. Hyperandrogenemia and insulin sensitivity were significantly improved with the use of the two drugs. However, metabolic or hormonal markers for predicting the drug response could not be found.
Subject(s)
Female , Humans , Pregnancy , Amenorrhea , Anovulation , Glucose Clamp Technique , Glucose Tolerance Test , Gonadal Steroid Hormones , Hyperandrogenism , Hyperinsulinism , Infertility , Insulin , Insulin Resistance , Menstruation , Metformin , Polycystic Ovary Syndrome , Testosterone , Weight LossABSTRACT
In Alzheimer's disease there is obvious evidence of insulin resistance in the brain. Thiazolidinediones,a kind of insulin sensitizer,not only improves insulin sensitivity,but also decreases inflammation,promotes release and clearance of?-amyloid protein,all are beneficial to the improvement of memory.
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Nonalcoholic fatty liver disease(NAFLD)has become one of the most common liver diseases in the world.Considering the important role of insulin resistance in its pathogenic mechanisms,insulin sensitizers are becoming the promising pharmacological strategies for NAFLD.We collected and analyzed the relevant articles in recent years and found that pioglitazone,rosiglitazone and metformin could improve liver enzymes and insulin sensitivity of NAFLD.However,only pioglitazine was supported in ameliorating liver histology by envidences from randomized,double-blinded,controlled clinical trials.There were no much obvious adverse effects in NAFLD patients who received insulin senitizers.Small or medium samples and no more than 2 years of treatment course may be the major limitation of current studies.Future information derived from well-designed running trials will be useful in defining the clinical implications of insulin sensitizers in the treatment of NAFLD.
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PURPOSE: The aim of this study was to investigate treatment results, toxicity and efficacy of hyperfractionated radiation therapy combined with paclitaxel for paraaortic node recurrence in cervix cancer. MATERIALS AND METHODS: Between September 1997 to March 1999, 12 patients with paraaortic node recurrence in cervix cancer who previously received radical or postoperative radiotherapy were treated with hyperfractionated radiation therapy combined with paclitaxel. Of these, 2 patients who irradiated less than 30 Gy were excluded, 10 patients were eligible for this study. Median age was 5 1 years. Initial FlGO stage was 1 stage IB1, 2 stage IIA, 7 stage IIB. For initial treatment, 7 patients received radical radiotherapy and 3 received postoperative radiotherapy. The paraaortic field encompassed the gross recur rent disease with superior margin at T 12, and inferior margin was between L5 and S 1 with gap for previously pelvic radiation field. The radiation field was initially anterior and posterior opposed field followed by both lateral field. The daily dose was 1.2 Gy, twice daily fractions, and total radiotherapy dose was between 50.4 and 60 Gy(median, 58.8 Gy). Concurrent chemotherapy was done with paclitaxel as a radiosensitizer. Dose range was from 20 mg/m to 30 mg/m (median, 25 mg/m'), and cycle of chemotherapy was from 3 to 6 (median, 4.5 cycle). Follow-up period ranged from 3 to 21 months. RESULTS: Interval between initial diagnosis and paraaortic node recurrence was range from 2 to 63 months (median, 8 months). The 1 year overall survival rate and median survival were 75% and 9.5 months, respectively. The 1 year disease free survival rate and median disease free survival were 30% and 3 7 months, respectively. At 1 month after treatment, 4 (40%) achieved a complete response and 6 (63%) experienced a partial response and all patients showed response above the partial response. There was distant metastasis in 6 patients and pelvic node recurrence in 2 patients after paraaortic node irradialion. There was 2 patients with grade 3 to 4 leukopenia and 8 patients with grade 1 to 2 nausea/ vom ting which was usually tolerable with antiemetic drug. There was no chronic complication in abdomen and pelvis during follow up period. CONCLUSION: Hyperfractionated radiation therapy combined with paclitaxel as a radiosensitizer showed high response rate and few complication rate in paraaortic node recurrence in cervix cancer. Therefore, present results suggest that hyperfractionated radiation therapy combined with paclitaxel chemotherapy can be used as optimal treatment modality in this patients.
Subject(s)
Female , Humans , Abdomen , Cervix Uteri , Diagnosis , Disease-Free Survival , Drug Therapy , Follow-Up Studies , Leukopenia , Neoplasm Metastasis , Paclitaxel , Pelvis , Radiotherapy , Recurrence , Survival Rate , Tolnaftate , Uterine Cervical NeoplasmsABSTRACT
PURPOSE: To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. MATERIALS AND METHODS: From December 1996 to January 1999, 38 previously untreated patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3060 cGy), 900~1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000~3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. RESULTS: Hematolgic toxicity was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5%) treated with radiation therapy and cisplatin and one of 22 patients (4.5%) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7%) treated with radiation therapy and cisplatin and two of 22 patients (9.1%) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80% (16/20) for the radiation therapy alone group and 78% (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). CONCLUSION: This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable medically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.