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1.
Front Oncol ; 12: 939425, 2022.
Article in English | MEDLINE | ID: mdl-36439491

ABSTRACT

Background: The first-line chemotherapy for patients with RAS and BRAF wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors [bevacizumab, ramucirumab, and aflibercept (AFL)] carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies. Methods: FOLFIRI (irinotecan 180 mg/m2, l-leucovorin 200 mg/m2, bolus 5-FU 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi. Discussion: There is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy. Clinical trial registration: Japan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs011190006.

2.
Gan To Kagaku Ryoho ; 39(2): 289-92, 2012 Feb.
Article in Japanese | MEDLINE | ID: mdl-22333646

ABSTRACT

The patient was a 67-year-old male with type-3 gastric cancer from the upper body of the stomach to the cardia. An abdominal computed tomography scan revealed liver metastases(S8)(T2N0M0H1, Stage IV). The patient received neoadjuvant combined chemotherapy with S-1 and CDDP. S-1(120mg/body/day)was orally administered for 3 weeks followed by 2 drug-free weeks as a course, and CDDP(60mg/m2)was administered by intravenous infusion on day 8. After the second course, significant tumor reduction and disappearance of liver metastases resulted. Total gastrectomy, splenectomy, cholecystectomy, and D2 nodal dissection were performed. The histological diagnosis revealed no metastases in all lymph nodes: Stage I B. The combined neoadjuvant chemotherapy with S-1 and CDDP can be considered an effective treatment for advanced gastric cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Liver Neoplasms/drug therapy , Stomach Neoplasms/drug therapy , Aged , Biopsy , Cisplatin/administration & dosage , Drug Combinations , Humans , Liver Neoplasms/secondary , Male , Neoadjuvant Therapy , Neoplasm Staging , Oxonic Acid/administration & dosage , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tegafur/administration & dosage , Tomography, X-Ray Computed
4.
Oncol Rep ; 24(5): 1307-13, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20878125

ABSTRACT

Chemoradiotherapy is a useful treatment strategy in patients with locally advanced cancers. In particular, combination of 5-fluorouracil (5-FU) with X-ray irradiation is effective for the treatment of some types of gastrointestinal cancers. We investigated the antitumor effects of combination treatment with X-ray and S-1, a unique formulation of 5-FU, on human cancer xenografts in nude mice and compared the efficacy of this treatment to that of radiotherapy combined with cisplatin, UFT, another oral 5-FU prodrug, and intravenous 5-FU. Tumors implanted into the left hind legs of mice were treated with a dose of 2 or 5 Gy X-ray irradiation on days 1 and 8, and S-1, UFT and 5-FU were administered for 14 days. The efficacy of combined treatment with 8.3 mg/kg S-1 and 2 Gy X-ray irradiation in treating non-small cell lung cancer xenografts (Lu-99 and LC-11) was significantly higher than that of treatment with S-1 alone or 2 Gy X-ray irradiation alone, and the antitumor activity of combined treatment was similar to that of 5 Gy X-ray irradiation alone. Although 8.3 mg/kg S-1 and 17.5 mg/kg UFT had equivalent antitumor activity; the antitumor efficacy of combination treatment with S-1 and 2 Gy X-ray irradiation on LC-11 tumors was significantly higher than that of combination treatment with UFT and 2 Gy X-ray irradiation. Combination treatment with S-1 and X-ray irradiation was also more effective against pancreatic tumors than combination treatment with intravenous 5-FU and X-ray irradiation. To elucidate the reason for the increased antitumor efficacy of combination treatment with S-1 and X-ray irradiation, the antitumor effect of gimeracil, one of the components of S-1, was tested in combination with 2 Gy X-ray irradiation. These experiments demonstrated that gimeracil enhanced the efficacy of X-ray irradiation against lung as well as head and neck cancer xenografts in a dose-dependent manner. Furthermore, we observed decreased expression of γ-H2AX protein, a marker of DNA repair, in LC-11 tumors treated with X-ray irradiation and gimeracil compared to that observed in tumors treated with X-ray irradiation alone, suggesting that gimeracil may inhibit rapid repair of X-ray-induced DNA damage in tumors. The present study suggests that chemoradiotherapy using S-1 acts through a novel mechanism and may prove useful in treating patients with locally advanced cancers whose disease progression is difficult to control using chemotherapy alone.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Neoplasms/drug therapy , Neoplasms/radiotherapy , Pyridines/pharmacology , Animals , Cell Line, Tumor , Combined Modality Therapy , Drug Combinations , Fluorouracil/administration & dosage , Fluorouracil/pharmacology , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Oxonic Acid/administration & dosage , Oxonic Acid/pharmacology , Pyridines/administration & dosage , Radiation-Sensitizing Agents/pharmacology , Tegafur/administration & dosage , Tegafur/pharmacology , Whole-Body Irradiation , Xenograft Model Antitumor Assays
5.
Clin Drug Investig ; 30(4): 243-9, 2010.
Article in English | MEDLINE | ID: mdl-20225907

ABSTRACT

BACKGROUND: Combined therapy with irinotecan/fluorouracil/levoleucovorin (calcium levofolinate) [IFL] has lost its position as the standard regimen for metastatic colorectal cancer because its toxicity and effectiveness have become controversial. OBJECTIVE: To (i) identify the optimal regimen for IFL therapy in terms of irinotecan dosage, and (ii) determine the maximum tolerated dose and efficacy of the modified-IFL regimen in patients with histologically confirmed advanced colorectal cancer. METHODS: In a phase I study, nine patients with advanced colorectal cancer received IFL treatment modified such that irinotecan was administered every 2 weeks, as opposed to the more toxic once-weekly administration. The study evaluated three escalating dose levels of irinotecan (100, 125 and 150 mg/m(2)). Each treatment cycle consisted of irinotecan on days 1 and 15; fluorouracil 600 mg/m(2) on days 1, 8, 15 and 22; and levoleucovorin 250 mg/m(2) on days 1, 8, 15 and 22. Data from the phase I study were used to determine the recommended dose of irinotecan for the phase II study. The latter study evaluated the effectiveness (overall response rate, median time to disease progression and median survival time) and tolerability of this modified-IFL therapy as ambulatory treatment in 22 patients with advanced colorectal cancer. RESULTS: The dose-limiting toxicity of irinotecan was grade 3 neutropenia, which occurred in three patients at dose level 2 (125 mg/m(2)); furthermore, a fourth patient developed grade 4 neutropenia at this dose level. Therefore, 125 mg/m(2) was considered to be the maximum tolerated dose, and the dose of irinotecan for the phase II study was set at 100 mg/m(2). Fourteen patients achieved partial response using this modified-IFL regimen, and the overall response rate was 63.6% (95% CI 43.5, 83.7). The median time to progression was 197 days (range 111-283 days) and the median survival time was 414 days (95% CI 116, 712). Toxicities were acceptable and manageable. CONCLUSIONS: Modified-IFL therapy is a practical, effective and tolerable option for ambulatory treatment of advanced colorectal cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adolescent , Adult , Aged , Ambulatory Care , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/mortality , Colorectal Neoplasms/physiopathology , Disease Progression , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Metastasis , Survival Rate , Treatment Outcome , Young Adult
6.
Health Care Women Int ; 28(9): 828-42, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17907010

ABSTRACT

This study investigates the changes in the quality of life (QOL) of gynecological patients undergoing surgery, and the relationship between these changes and clinical/demographic factors. Ninety patients were examined on three occasions using the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-core30 (EORTC QLQ-C30). Although the global QOL and physical function decreased before discharge, the emotional function was lowest before surgery. There was no difference between the benign and malignancy groups in most QOL subscales. With regard to the relationship between global QOL and physical function before discharge and other demographic/clinical factors, multiple regression analysis suggested that these were explained by employment status, benign/malignancy, region of tumor, chemotherapy, postoperative complication, and psychological symptoms during hospitalization.


Subject(s)
Genital Neoplasms, Female/psychology , Genital Neoplasms, Female/surgery , Quality of Life/psychology , Women's Health , Adult , Analysis of Variance , Anxiety/etiology , Depression/etiology , Female , Genital Neoplasms, Female/complications , Humans , Inpatients/statistics & numerical data , Japan , Middle Aged , Perioperative Care/psychology , Psychometrics/instrumentation , Sickness Impact Profile , Surveys and Questionnaires
7.
Psychiatry Clin Neurosci ; 61(1): 84-93, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17239044

ABSTRACT

The aim of the present study was to investigate changes in emotional state and the relationship between emotional state and demographic/clinical factors and coping style among gynecologic patients undergoing surgery. Using the Japanese version of the Profile of Mood States (POMS), 90 patients (benign disease: 32, malignancy: 58) were examined on three occasions: before surgery, before discharge, and 3 months after discharge. They were also examined using the Coping Inventory for Stressful Situations (CISS) on one occasion before discharge. The scores for the subscales depression, anger, and confusion were the highest after discharge while those for anxiety were the highest before surgery. The average scores of the POMS subscales for all subjects were within the normal range. With regard to the relationship between these emotional states and other factors, multiple regressions showed that the principal determinants of anxiety before surgery were religious belief, psychological symptoms during hospitalization and emotion-oriented (E) coping style; further, it was found that depression after discharge could be explained by chemotherapy, duration of hospitalization, and E coping style. The principal determinants of anger after discharge and vigor before surgery were length of education and E coping style, and severity of disease, chemotherapy, E coping style and task-oriented coping style, respectively. Those of post-discharge fatigue and confusion were length of education, psychological symptoms, and E coping style. In summary it is suggested that the following should be taken into account in patients undergoing gynecologic surgery: anxiety before surgery, depression, anger, and confusion after surgery, including coping styles.


Subject(s)
Adaptation, Psychological/physiology , Emotions , Gynecologic Surgical Procedures/psychology , Adult , Affect , Aged , Anger/physiology , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Fatigue/psychology , Female , Genital Diseases, Female/psychology , Genital Diseases, Female/surgery , Genital Neoplasms, Female/psychology , Genital Neoplasms, Female/surgery , Humans , Length of Stay , Longitudinal Studies , Middle Aged , Psychological Tests , Regression Analysis , Socioeconomic Factors
8.
Gastric Cancer ; 9(1): 36-43, 2006.
Article in English | MEDLINE | ID: mdl-16557435

ABSTRACT

BACKGROUND: Both paclitaxel (TXL) and cisplatin (CDDP) show efficacy against gastric cancer. The aim of this phase I-II study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and efficacy of combination chemotherapy with these two agents. METHODS: Nineteen patients entered the phase I part of the study, and 21 patients entered the phase II part. TXL infusions were administered on days 1 and 15, with a fixed 3mg/m2 dose of CDDP. RESULTS: In the phase I part of the study, we determined dose level 5, which represented a TXL dose of 18 mg/m2, with CDDP 3 mg/m2, to be the MTD. The recommended dose (RD) was level 4, with a TXL dose of 16 mg/m2 with CDDP, 3 mg/m2. In the phase II part of the study, the response rate was 25.0%; five patients had a partial response, seven had stable disease, 6 had progressive disease, and 2 were not evaluable. Grade 3 or 4 neutropenia was the most common adverse event and occurred in 65% of the patients. During treatment, 25% of the patients received granulocyte colony-stimulating factor, but febrile neutropenia was not shown in any of the patients. Major nonhematological toxicities were nausea/vomiting, anorexia, fatigue, alopecia, and sensory neuropathy. Adverse reactions of grade 3 or 4 were shown by two patients, one with anorexia (5%) and the other with sensory neuropathy (5%). CONCLUSION: The RD was determined to be TXL 14 mg/m2, with CDDP 3 mg/m2.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Intestinal Neoplasms/drug therapy , Stomach Neoplasms/drug therapy , Aged , Cisplatin/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Intestinal Neoplasms/surgery , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Stomach Neoplasms/surgery , Survival Rate
9.
Int J Cancer ; 119(4): 783-91, 2006 Aug 15.
Article in English | MEDLINE | ID: mdl-16557585

ABSTRACT

We have recently demonstrated in a Phase I/II study that combination chemotherapy with docetaxel (TXT) and S-1 is active against metastatic gastric carcinomas. To elucidate the mechanisms underlying the synergistic effects of these drugs, both the growth inhibitory effects and the expression profiles of enzymes involved in fluorouracil (5-FU) metabolism were examined in vitro and in vivo. TXT alone and in combination with 5-FU inhibited the growth of each of the 5 gastric cancer cell lines that we examined (TMK-1, and MKN-1, -28, -45 and -74), in a time- and dose-dependent manner. Moreover, striking synergistic effects were observed in TMK-1 cells in vitro with IC50 values of between 4.73 and 0.61 nM 5-FU. Furthermore, in TMK-1 xenografts, 5-FU/TXT cotreatments exhibited synergistic antitumor effects. The combination of S-1 and TXT, however, exhibited greater growth-inhibitory effects than the 5-FU/TXT cotreatments. The mechanisms underlying these synergistic effects of S-1 and TXT were examined by expression and activity analyses of the 5-FU metabolic enzymes. The expression of thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) were decreased 50 and 73% of control levels, respectively, and that of orotate phosphorybosyl transferase (OPRT) was increased by 3.9-fold at the protein level. These findings suggested that biochemical modulation of the 2 drugs had occurred, which was further confirmed by the results of the activity assays. These data strongly indicate that a combination chemotherapy of TXT and S-1 is effective against gastric carcinomas and is therefore a good candidate as a standard chemotherapeutic strategy in treating these tumors.


Subject(s)
Fluorouracil/metabolism , Oxonic Acid/pharmacology , Stomach Neoplasms/enzymology , Taxoids/pharmacology , Tegafur/pharmacology , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Dihydrouracil Dehydrogenase (NADP)/metabolism , Docetaxel , Drug Combinations , Drug Synergism , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Mice , Mice, Nude , Multienzyme Complexes/genetics , Multienzyme Complexes/metabolism , Orotate Phosphoribosyltransferase/genetics , Orotate Phosphoribosyltransferase/metabolism , Orotidine-5'-Phosphate Decarboxylase/genetics , Orotidine-5'-Phosphate Decarboxylase/metabolism , Stomach Neoplasms/pathology , Thymidylate Synthase/metabolism , Xenograft Model Antitumor Assays
10.
Jpn J Clin Oncol ; 35(12): 714-9, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16303791

ABSTRACT

BACKGROUND: Previously we reported that immunohistochemical examination of p53, bcl-2, glutathione S-transferase-pi (GST-pi), thymidylate synthase (TS) and vascular endothelial growth factor (VEGF) in biopsy samples was a useful method for predicting clinical outcome of gastric cancer patients treated with 5-fluorouracil and cisplatin. Here, we investigated if these biological markers can predict chemoresponse and survival of unresectable gastric cancer patients treated with irinotecan and cisplatin. METHODS: The subjects were 55 unresectable gastric cancer patients treated with irinotecan (70 mg/m(2), Days 1 and 15) and cisplatin (80 mg/m(2), Day 1). Expression of p53, bcl-2, VEGF was examined immunohistochemically in biopsy samples. RESULTS: The overall response rate and the median survival time were 55% (30/55) and 321 days, respectively. Thirty patients with intestinal-type adenocarcinoma survived longer than 25 patients with diffuse-type (median survival time: 446, 259 days, P = 0.013). The favorable phenotypes for chemoresponse were p53-negative, bcl-2-negative and VEGF-positive, which were in accordance with previous findings. The response rate was significantly correlated with the total number of these favorable phenotypes (P = 0.043). The 39 patients having 2 or 3 favorable phenotypes (p53-negative, bcl-2-negative and VEGF-positive) survived longer than the remaining 16 patients (median survival time: 444, 259 days, P = 0.021). In the Cox model, the number of the favorable phenotypes showed a tendency to correlate with survival after adjustment for potentially prognostic factors such as histological type or performance status (P = 0.070). CONCLUSIONS: Immunohistochemical examination of biological markers may be useful in predicting the clinical outcome of unresectable gastric cancer patients treated with irinotecan and cisplatin.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Stomach Neoplasms/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adult , Aged , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Cisplatin/administration & dosage , Drug Administration Schedule , Female , Glutathione S-Transferase pi/analysis , Humans , Irinotecan , Male , Middle Aged , Predictive Value of Tests , Prognosis , Proto-Oncogene Proteins c-bcl-2/analysis , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Tumor Suppressor Protein p53/analysis , Vascular Endothelial Growth Factor A/analysis
11.
Jpn J Clin Oncol ; 35(2): 88-9, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15709093

ABSTRACT

We have previously reported on phase I/II studies of irinotecan plus S-1 therapy for advanced gastric cancer. Based on the safety and efficacy data that were obtained, this phase II study was planned to assess the efficacy of irinotecan plus S-1 for patients with advanced colorectral cancer. A total of 40 patients are enrolled at 13 medical institutions. The objective of this study was to establish a useful chemotherapy regimen for an out-patient setting.


Subject(s)
Adenocarcinoma/drug therapy , Ambulatory Care , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Administration, Oral , Adolescent , Adult , Aged , Camptothecin/administration & dosage , Drug Administration Schedule , Drug Combinations , Humans , Irinotecan , Middle Aged , Oxonic Acid/administration & dosage , Pyridines/administration & dosage , Tegafur/administration & dosage
12.
J Med Dent Sci ; 51(1): 99-104, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15137471

ABSTRACT

Hyperactivation and acrosome reaction are prerequisite steps for sperm to be able to fertilize an oocyte. In mammals, hyperactivation is defined as a movement pattern seen in spermatozoa at the site and time of fertilization. The objectives of the present experiments were to analyze the process of hyperactivation and to investigate its relationship with progesterone evoked intracellular calcium concentration ([Ca2+]i) increase and their implications with infertility. After capacitation the sperm from patients, when compared with donor's sperm, showed decreased percentage of hyperactivated sperm, molitily, progressive motility, and curvilinear velocity (VCL). On the other hand, the linearity (LIN) was increased. Amplitude of lateral head displacement (ALH) and [Ca2+]i increase (peak and plateau from baseline) showed good correlation in patients with infertility. These data suggest that impaired hyperactivation might be involved in the pathophysiology of infertility.


Subject(s)
Fura-2/analogs & derivatives , Infertility, Male/physiopathology , Sperm Motility/physiology , Sperm-Ovum Interactions/physiology , Acrosome Reaction/physiology , Calcium/pharmacokinetics , Fluorescent Dyes , Humans , Male , Progesterone/pharmacology , Sperm Capacitation/physiology , Sperm Count , Sperm Head/physiology , Sperm Head/ultrastructure , Spermatozoa/drug effects , Spermatozoa/metabolism , Time Factors
13.
Oncology ; 64(3): 232-6, 2003.
Article in English | MEDLINE | ID: mdl-12697963

ABSTRACT

OBJECTIVES: To evaluate the efficacy and safety of capecitabine in patients with advanced or recurrent gastric cancer, we conducted a pilot phase II study in Japan. METHODS: Patients with advanced or recurrent gastric cancer were given oral capecitabine 828 mg/m(2) twice daily for 3 weeks, followed by 1 week of no treatment. Two or more cycles were administered. From July 1996 to December 1997, 32 patients were enrolled in the study. The response to capecitabine was evaluated in 31 patients, excluding 1 found to be ineligible. RESULTS: The overall response rate was 19.4% (6/31, 95% confidence interval: 7.5-37.5%). The median duration of response was 124.5 days, the median time to disease progression 85.0 days, and the median survival time 247.5 days. Drug-related adverse events of grade 3 or higher were infrequent: in 2 patients (6.3%) total bilirubin concentration increased, and 1 patient (3.1%) each had elevation of GOT, anemia, lymphopenia, increased creatinine, and hand-foot syndrome. No patient had gastrointestinal toxicity of grade 3 or higher. CONCLUSION: Capecitabine was suggested to be safe and effective in the treatment of advanced or recurrent gastric cancer. Further phase II studies of capecitabine on a large scale are warranted.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Stomach Neoplasms/drug therapy , Administration, Oral , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Capecitabine , Deoxycytidine/administration & dosage , Drug Administration Schedule , Female , Fluorouracil/analogs & derivatives , Humans , Japan , Male , Middle Aged , Pilot Projects , Stomach Neoplasms/pathology , Treatment Outcome
15.
FEBS Lett ; 516(1-3): 229-33, 2002 Apr 10.
Article in English | MEDLINE | ID: mdl-11959138

ABSTRACT

To know the function of the Ca2+ channel containing alpha(1)2.3 (alpha1E) subunit (Ca(v)2.3 channel) in spermatozoa, we analyzed Ca2+ transients and sperm motility using a mouse strain lacking Ca(v)2.3 channel. The averaged rising rates of Ca2+ transients induced by alpha-D-mannose-bovine serum albumin in the head region of Ca(v)2.3-/- sperm were significantly lower than those of Ca(v)2.3+/+ sperm. A computer-assisted sperm motility assay revealed that straight-line velocity and linearity were greater in Ca(v)2.3-/- sperm than those in Ca(v)2.3+/+ sperm. These results suggest that the Ca(v)2.3 channel plays some roles in Ca2+ transients and the control of flagellar movement.


Subject(s)
Calcium Channels/physiology , Cation Transport Proteins , Sperm Motility/physiology , Animals , Calcium Channels/genetics , Calcium Channels, R-Type , Calcium Signaling/genetics , Calcium Signaling/physiology , In Vitro Techniques , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Movement/physiology , Sperm Motility/genetics , Sperm Tail/physiology
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