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1.
Int J Mol Sci ; 25(8)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38674080

ABSTRACT

Cellular hypoxia, detectable in up to 80% of non-small cell lung carcinoma (NSCLC) tumors, is a known cause of radioresistance. High linear energy transfer (LET) particle radiation might be effective in the treatment of hypoxic solid tumors, including NSCLC. Cellular hypoxia can activate nuclear factor κB (NF-κB), which can modulate radioresistance by influencing cancer cell survival. The effect of high-LET radiation on NF-κB activation in hypoxic NSCLC cells is unclear. Therefore, we compared the effect of low (X-rays)- and high (12C)-LET radiation on NF-κB responsive genes' upregulation, as well as its target cytokines' synthesis in normoxic and hypoxic A549 NSCLC cells. The cells were incubated under normoxia (20% O2) or hypoxia (1% O2) for 48 h, followed by irradiation with 8 Gy X-rays or 12C ions, maintaining the oxygen conditions until fixation or lysis. Regulation of NF-κB responsive genes was evaluated by mRNA sequencing. Secretion of NF-κB target cytokines, IL-6 and IL-8, was quantified by ELISA. A greater fold change increase in expression of NF-κB target genes in A549 cells following exposure to 12C ions compared to X-rays was observed, regardless of oxygenation status. These genes regulate cell migration, cell cycle, and cell survival. A greater number of NF-κB target genes was activated under hypoxia, regardless of irradiation status. These genes regulate cell migration, survival, proliferation, and inflammation. X-ray exposure under hypoxia additionally upregulated NF-κB target genes modulating immunosurveillance and epithelial-mesenchymal transition (EMT). Increased IL-6 and IL-8 secretion under hypoxia confirmed NF-κB-mediated expression of pro-inflammatory genes. Therefore, radiotherapy, particularly with X-rays, may increase tumor invasiveness in surviving hypoxic A549 cells.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , NF-kappa B , Humans , NF-kappa B/metabolism , A549 Cells , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/radiotherapy , Lung Neoplasms/pathology , Lung Neoplasms/genetics , X-Rays , Gene Expression Regulation, Neoplastic/radiation effects , Linear Energy Transfer , Cell Hypoxia/radiation effects , Carbon , Cell Survival/radiation effects , Radiation Tolerance , Interleukin-8/metabolism , Interleukin-8/genetics
2.
Int J Mol Sci ; 25(2)2024 Jan 13.
Article in English | MEDLINE | ID: mdl-38256084

ABSTRACT

Hypoxia-induced radioresistance reduces the efficacy of radiotherapy for solid malignancies, including non-small cell lung cancer (NSCLC). Cellular hypoxia can confer radioresistance through cellular and tumor micro-environment adaptations. Until recently, studies evaluating radioresistance secondary to hypoxia were designed to maintain cellular hypoxia only before and during irradiation, while any handling of post-irradiated cells was carried out in standard oxic conditions due to the unavailability of hypoxia workstations. This limited the possibility of simulating in vivo or clinical conditions in vitro. The presence of molecular oxygen is more important for the radiotoxicity of low-linear energy transfer (LET) radiation (e.g., X-rays) than that of high-LET carbon (12C) ions. The mechanisms responsible for 12C ions' potential to overcome hypoxia-induced radioresistance are currently not fully understood. Therefore, the radioresistance of hypoxic A549 NSCLC cells following exposure to X-rays or 12C ions was investigated along with cell cycle progression and gene expression by maintaining hypoxia before, during and after irradiation. A549 cells were incubated under normoxia (20% O2) or hypoxia (1% O2) for 48 h and then irradiated with X-rays (200 kV) or 12C ions (35 MeV/n, LET ~75 keV/µm). Cell survival was evaluated using colony-forming ability (CFA) assays immediately or 24 h after irradiation (late plating). DNA double-strand breaks (DSBs) were analyzed using γH2AX immunofluorescence microscopy. Cell cycle progression was determined by flow cytometry of 4',6-diamidino-2-phenylindole-stained cells. The global transcription profile post-irradiation was evaluated by RNA sequencing. When hypoxia was maintained before, during and after irradiation, hypoxia-induced radioresistance was observed only in late plating CFA experiments. The killing efficiency of 12C ions was much higher than that of X-rays. Cell survival under hypoxia was affected more strongly by the timepoint of plating in the case of X-rays compared to 12C ions. Cell cycle arrest following irradiation under hypoxia was less pronounced but more prolonged. DSB induction and resolution following irradiation were not significantly different under normoxia and hypoxia. Gene expression response to irradiation primarily comprised cell cycle regulation for both radiation qualities and oxygen conditions. Several PI3K target genes involved in cell migration and cell motility were differentially upregulated in hypoxic cells. Hypoxia-induced radioresistance may be linked to altered cell cycle response to irradiation and PI3K-mediated changes in cell motility and migration in A549 cells rather than less DNA damage or faster repair.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/radiotherapy , A549 Cells , Lung Neoplasms/radiotherapy , Hypoxia , Radiation Tolerance , Oxygen , Ions , Phosphatidylinositol 3-Kinases , Tumor Microenvironment
3.
Cancers (Basel) ; 15(9)2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37173939

ABSTRACT

Hypoxia occurs in 80% of non-small cell lung carcinoma (NSCLC) cases, leading to treatment resistance. Hypoxia's effects on NSCLC energetics are not well-characterized. We evaluated changes in glucose uptake and lactate production in two NSCLC cell lines under hypoxia in conjunction with growth rate and cell cycle phase distribution. The cell lines A549 (p53 wt) and H358 (p53 null) were incubated under hypoxia (0.1% and 1% O2) or normoxia (20% O2). Glucose and lactate concentrations in supernatants were measured using luminescence assays. Growth kinetics were followed over seven days. Cell nuclei were stained with DAPI and nuclear DNA content was determined by flow cytometry to determine cell cycle phase. Gene expression under hypoxia was determined by RNA sequencing. Glucose uptake and lactate production under hypoxia were greater than under normoxia. They were also significantly greater in A549 compared to H358 cells. Faster energy metabolism in A549 cells was associated with a higher growth rate in comparison to H358 cells under both normoxia and hypoxia. In both cell lines, hypoxia significantly slowed down the growth rate compared to proliferation under normoxic conditions. Hypoxia led to redistribution of cells in the different cycle phases: cells in G1 increased and the G2 population decreased. Glucose uptake and lactate production increase under hypoxia in NSCLC cells indicated greater shunting of glucose into glycolysis rather than into oxidative phosphorylation compared to normoxia, making adenosine triphosphate (ATP) production less efficient. This may explain the redistribution of hypoxic cells in the G1 cell cycle phase and the time increase for cell doubling. Energy metabolism changes were more prominent in faster-growing A549 cells compared to slower-growing H358 cells, indicating possible roles for the p53 status and inherent growth rate of different cancer cells. In both cell lines, genes associated with cell motility, locomotion and migration were upregulated under chronic hypoxia, indicating a strong stimulus to escape hypoxic conditions.

4.
Front Public Health ; 11: 1063250, 2023.
Article in English | MEDLINE | ID: mdl-37089489

ABSTRACT

Introduction: Exposure to space conditions during crewed long-term exploration missions can cause several health risks for astronauts. Space radiation, isolation and microgravity are major limiting factors. The role of astrocytes in cognitive disturbances by space radiation is unknown. Astrocytes' response toward low linear energy transfer (LET) X-rays and high-LET carbon (12C) and iron (56Fe) ions was compared to reveal possible effects of space-relevant high-LET radiation. Since astronauts are exposed to ionizing radiation and microgravity during space missions, the effect of simulated microgravity on DNA damage induction and repair was investigated. Methods: Primary murine cortical astrocytes were irradiated with different doses of X-rays, 12C and 56Fe ions at the heavy ion accelerator GSI. DNA damage and repair (γH2AX, 53BP1), cell proliferation (Ki-67), astrocytes' reactivity (GFAP) and NF-κB pathway activation (p65) were analyzed by immunofluorescence microscopy. Cell cycle progression was investigated by flow cytometry of DNA content. Gene expression changes after exposure to X- rays were investigated by mRNA-sequencing. RT-qPCR for several genes of interest was performed with RNA from X-rays- and heavy-ion-irradiated astrocytes: Cdkn1a, Cdkn2a, Gfap, Tnf, Il1ß, Il6, and Tgfß1. Levels of the pro inflammatory cytokine IL-6 were determined using ELISA. DNA damage response was investigated after exposure to X-rays followed by incubation on a 2D clinostat to simulate the conditions of microgravity. Results: Astrocytes showed distinct responses toward the three different radiation qualities. Induction of radiation-induced DNA double strand breaks (DSBs) and the respective repair was dose-, LET- and time-dependent. Simulated microgravity had no significant influence on DNA DSB repair. Proliferation and cell cycle progression was not affected by radiation qualities examined in this study. Astrocytes expressed IL-6 and GFAP with constitutive NF-κB activity independent of radiation exposure. mRNA sequencing of X-irradiated astrocytes revealed downregulation of 66 genes involved in DNA damage response and repair, mitosis, proliferation and cell cycle regulation. Discussion: In conclusion, primary murine astrocytes are DNA repair proficient irrespective of radiation quality. Only minor gene expression changes were observed after X-ray exposure and reactivity was not induced. Co-culture of astrocytes with microglial cells, brain organoids or organotypic brain slice culture experiments might reveal whether astrocytes show a more pronounced radiation response in more complex network architectures in the presence of other neuronal cell types.


Subject(s)
Astrocytes , NF-kappa B , Animals , Mice , Astrocytes/metabolism , Interleukin-6 , Ions , Brain , RNA, Messenger , DNA
5.
Int J Mol Sci ; 22(24)2021 Dec 16.
Article in English | MEDLINE | ID: mdl-34948324

ABSTRACT

Nuclear factor κB (NF-κB) activation might be central to heavy ion-induced detrimental processes such as cancer promotion and progression and sustained inflammatory responses. A sensitive detection system is crucial to better understand its involvement in these processes. Therefore, a DD-tdTomato fluorescent protein-based reporter system was previously constructed with human embryonic kidney (HEK) cells expressing DD-tdTomato as a reporter under the control of a promoter containing NF-κB binding sites (HEK-pNFκB-DD-tdTomato-C8). Using this reporter cell line, NF-κB activation after exposure to different energetic heavy ions (16O, 95 MeV/n, linear energy transfer-LET 51 keV/µm; 12C, 95 MeV/n, LET 73 keV/µm; 36Ar, 95 MeV/n, LET 272 keV/µm) was quantified considering the dose and number of heavy ions hits per cell nucleus that double NF-κB-dependent DD-tdTomato expression. Approximately 44 hits of 16O ions and ≈45 hits of 12C ions per cell nucleus were required to double the NF-κB-dependent DD-tdTomato expression, whereas only ≈3 hits of 36Ar ions were sufficient. In the presence of Shield-1, a synthetic molecule that stabilizes DD-tdTomato, even a single particle hit of 36Ar ions doubled NF-κB-dependent DD-tdTomato expression. In conclusion, stabilization of the reporter protein can increase the sensitivity for NF-κB activation detection by a factor of three, allowing the detection of single particle hits' effects.


Subject(s)
Heavy Ions/adverse effects , NF-kappa B/metabolism , Technology/methods , Cell Line , Cell Nucleus/drug effects , Cell Nucleus/metabolism , HEK293 Cells , Humans , Luminescent Proteins/metabolism , Promoter Regions, Genetic/drug effects
6.
Photodiagnosis Photodyn Ther ; 33: 102192, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33508501

ABSTRACT

Refractive index (RI) is a characteristic optical variable that controls the propagation of light in the medium (e.g., biological tissues). Basic research with the aim to investigate the RI of biological tissues is of paramount importance for biomedical optics and associated applications. Herein, we reviewed and summarized the RI data of biological tissues and the associated insights. Different techniques for the measurement of RI of biological tissues are also discussed. Moreover, several examples of the RI applications from basic research, clinics and optics industry are outlined. This study may provide a comprehensive reference for RI data of biological tissues for the biomedical research and beyond.


Subject(s)
Photochemotherapy , Refractometry , Photochemotherapy/methods , Photosensitizing Agents
7.
Photodiagnosis Photodyn Ther ; 33: 102096, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33188939

ABSTRACT

Cell refractive index (RI) is an intrinsic optical parameter that governs the propagation of light (i.e., scattering and absorption) in the cell matrix. The RI of cell is sensitively correlated with its mass distribution and thereby has the capability to provide important insights for diverse biological models. Herein, we review the cell refractive index and the fundamental models for measurement of cell RI, summarize the published RI data of cell and cell organelles and discuss the associated insights. Illustrative applications of cell RI in cell biology are also outlined. Finally, future research trends and applications of cell RI, including novel imaging techniques, reshaping flow cytometry and microfluidic platforms for single cell manipulation are discussed. The rapid technological advances in optical imaging integrated with microfluidic regime seems to enable deeper understanding of subcellular dynamics with high spatio-temporal resolution in real time.


Subject(s)
Photochemotherapy , Refractometry , Models, Biological , Optical Imaging , Photochemotherapy/methods , Photosensitizing Agents
8.
Acta Clin Croat ; 59(2): 216-222, 2020 Jun.
Article in English | MEDLINE | ID: mdl-33456107

ABSTRACT

In colorectal carcinoma, carcinoembryonic antigen (CEA) is a recommended marker for surveillance after curative resection. The aim of the present study was to determine the association of preoperative CEA with recurrence of colorectal carcinoma in our population. The study included 55 patients with all operable stages of colorectal adenocarcinoma treated during the 2012-2014 period, evaluated retrospectively and followed-up for recurrence for 2 years. Data on the baseline (preoperative) CEA levels were retrieved from patient files. On data analysis, SPSS 16.0 was used. In patients with normal preoperative CEA, the rate of recurrence was significantly low (p=0.008) and the likelihood of no recurrence 1.55-fold greater as compared to patients with raised initial CEA levels (p=0.028). In patients with raised preoperative CEA, the risk of recurrence was 5.26-fold greater as compared to those with normal CEA levels (p=0.028). A significant weak positive correlation (rs=0.297) was found between raised CEA and recurrence. A highly significant (p=0.002) moderate positive correlation was recorded in patients aged <50 and moderate positive correlation of borderline significance in males (rs=0.324, p=0.058). Sensitivity was 94.4% and specificity 32.4% in predicting recurrence. Accordingly, preoperative elevated CEA showed a significant weak positive correlation with recurrence while normal preoperative CEA moderately decreased the likelihood of recurrence.


Subject(s)
Carcinoembryonic Antigen , Colorectal Neoplasms , Neoplasm Recurrence, Local , Carcinoembryonic Antigen/analysis , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Retrospective Studies
9.
Turk J Med Sci ; 50(1): 291-297, 2020 04 09.
Article in English | MEDLINE | ID: mdl-31655504

ABSTRACT

Background/aim/AIM: Smokeless tobacco has been associated with oral cavity cancer for several decades. The incidence of oral cavity cancer is higher in some parts of the world especially South and South-East Asia including Pakistan. The aim of current study was to evaluate the risk of oral cavity cancer among smokeless tobacco users in our country. Materials and methodsAND METHODS: A case-control study was conducted between November 2016 and September 2017. Patients diagnosed with oral cavity cancer receiving treatment were included as cases and the attendants of various cancer patients visiting the hospital during the study period were included in the study as controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated and all reported P-values were considered significant at < 0.05. Results: The crude OR for the "ever smokeless tobacco users" among cases and controls came out to be 4.98 (95%CI; 2.76­9.01). The OR for snuff users among cases and controls was 4.82 (95%CI; 2.37­9.80) and that for betel leaf users was 4.42 (95%CI; 1.66­11.91) after adjusting for smoking and age. Conclusion: Our study provided strong evidence for snuff and betel leaf to be independent risk factors for oral cavity cancer.


Subject(s)
Mouth Neoplasms/etiology , Tobacco Use/adverse effects , Tobacco, Smokeless , Adult , Aged , Case-Control Studies , Humans , Male , Middle Aged , Mouth , Odds Ratio , Pakistan , Risk Factors , Young Adult
10.
Cureus ; 11(5): e4757, 2019 May 25.
Article in English | MEDLINE | ID: mdl-31363438

ABSTRACT

Introduction One of the common causes of chronic sinusitis is a fungal infection, and there are various types of fungal rhinosinusitis (FRS). Missed diagnosis of occasional granulomatous invasion of fungal sinusitis can lead to involvement in the central nervous system. The aim of this study is to determine the frequency of granulomatous invasive fungal sinusitis (GIFS) in patients with clinical suspicion of chronic FRS. Methods We conducted a descriptive cross-sectional study in the Department of Ear, Nose and Throat (ENT), Nishtar Hospital, Multan from January 1, 2017 to July 1, 2018. Eighty-one patients with chronic FRS participated in the study. After informed consent, nasal tissue was biopsied for granulomatous fungal invasion. Results The frequency of GIFS was 29.6% (n=24) in this study. The significant risk factors included duration of chronic FRS for more than 12 weeks, history of diabetes mellitus, and living status as rural. Conclusion GIFS is a common complication in patients with clinical suspicion of chronic FRS. Nasal biopsy should be a common practice among patients of chronic FRS who have a long duration of disease and a history of diabetes mellitus.

11.
J Coll Physicians Surg Pak ; 29(4): 356-360, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30925961

ABSTRACT

OBJECTIVE: To find the epidemiology and risk factors of sinonasal tumors and treatment outcomes in squamous cell carcinoma. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: The Institute of Nuclear Medicine and Oncology Lahore (INMOL), Lahore, from May 2016 to March 2017. METHODOLOGY: All histopathologically proven cases of paranasal sinuses and nasal cavity were selected from the hospital record for epidemiological analysis. Survival outcomes of patients with squamous cell histopathology were determined, which is commonly occurring type. Relevant information was obtained from patient record and telephone communication. The data were analysed using SPSS V.20. RESULTS: Sinonasal malignancies are rare, making (n=81) 0.2% of all registered tumors; out of which, 46 (56.7%) had squamous cell histology. Median age was 50.0 years (IQR: 60.7-40.0) with male predominance (1.7:1). Most of patients presented at advanced stage, T3/ T4 in more than two-thirds of cases, and associated with nodal metastasis in 43.5% of squamous cell carcinoma. In patients with squamous cell histology, median disease-free survival was 19.00 months (SE: 1.65, 95% CI, 15.75 - 22.25), median overall survival remained 34.00 months (SE: 1.84, 95% CI, 30.00 - 38.00). Nodal status had significant effect (p<0.001) on survival. Radiotherapy had significant effect on improved survival (p=0.001) and distant metastasis remained negative prognostic factor (p=0.001). Disease stage was also significantly associated with overall survival (Log Rank 0.014). Tumour size, surgery, chemotherapy, and chemoradiotherapy were not significantly associated with survival. Cumulative survival at 1, 2, and 3 years was 87%, 48% and 29%, respectively. CONCLUSION: Sinonasal malignancies are rare, advanced stage is common, and radiotherapy improves overall survival.


Subject(s)
Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/therapy , Paranasal Sinus Neoplasms/epidemiology , Paranasal Sinus Neoplasms/therapy , Adult , Aged , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Humans , Male , Middle Aged , Nasal Cavity/pathology , Otorhinolaryngologic Surgical Procedures , Pakistan/epidemiology , Paranasal Sinus Neoplasms/pathology , Survival Rate , Treatment Outcome
12.
Phys Med ; 47: 64-72, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29609820

ABSTRACT

Rheumatoid arthritis (RA) is a chronic inflammatory disease that can potentially damage the synovial joints. One of the effective treatment modality for RA is radiation synovectomy (RSV) where properly selected radionuclide is injected into the joint space, enabling controlled destruction of diseased synovial membrane via radiation exposure. Radiation dosimetry in RSV appears challenging due to the heterogeneous nature of synovial membrane, nonuniform distribution and leakage of radionuclide from the synovial cavity. This article reviews the dosimetric perspective pertaining to RSV. Specifically, characteristics of radionuclide for RSV and radiation dose to target and non-target (i.e., articular cartilage, bone, bloodstream, gonads, etc.) tissues of patient have been discussed. The personal dose Hp(0.07) to the hands of medical staff (i.e., radiochemist, therapist physician, nurse) may be considerably high due to handling of high specific activities (∼500 MBq/ml for Y-90); such doses are typically measured using thermoluminescence dosimeters (TLD) ring dosimeters and ranges from 1 to 21.5, 0.1 to 40 and 0.1 to 5 µSv/MBq for the radiochemist, therapist physician and the nurse, respectively. Methods to minimize radiation doses to the patient, medical staff and public are elaborated. Contamination risks and precautionary measures are also reported.


Subject(s)
Radiometry , Synovectomy/methods , Arthritis, Rheumatoid/surgery , Humans , Neoplasms, Radiation-Induced/etiology , Organs at Risk/radiation effects , Radiation Dosage , Synovectomy/adverse effects
13.
J Coll Physicians Surg Pak ; 28(4): 292-296, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29615170

ABSTRACT

OBJECTIVE: To determine the disease characteristics of testicular germ cell tumor, biochemical/radiological response to chemotherapy and common toxicity profile. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Institute of Nuclear Medicine and Oncology (INMOL), Lahore, from January 2010 to December 2013. METHODOLOGY: Fifty-one patients with histologically proven testicular germ cell tumor, who fulfilled the pre-defined eligibility criteria, were selected. Presenting symptoms and disease stage were studied. Patients were staged according to the AJCC 2010 staging criteria and prognosis was classified according to the IGCCCG Classification of Metastatic Germ Cell Cancer. Initial chemotherapy treatment was based upon the International Germ Cell Consensus Classification, 1997. Patients were also evaluated for chemotherapy-induced toxicity based on Common Toxicology Criteria version 4. SPSS version 16.0 was used for statistical analysis. RESULTS: Main presenting symptoms included testicular pain (37.3%), testicular swelling (25.5%), and abdominopelvic pain (11.8%). Most of the patients had mixed germ cell histology (p <0.001) and presented with advanced disease stage. Out of 51 patients, 41 (80.3%) achieved complete clinical remission after first line chemotherapy. All patients having complete response achieved 2-year survival and 37 (90.2%) had no evidence of recurrent disease. Four patients with recurrent disease achieved complete remission with second line chemotherapy. Five (9.8%) had partial response after first line chemotherapy while 2 (3.9%) progressed on treatment. All patients developed alopecia, 21 (41.1%) experienced other toxicities which were managed symptomatically and with minor dose modifications. CONCLUSION: Many patients with germ cell tumors presented with pain, and in an advanced stage, with mixed histology. Overall response rate was 90.2% with platinum-based chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Neoplasms, Germ Cell and Embryonal/drug therapy , Platinum , Testicular Neoplasms/drug therapy , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/administration & dosage , Bleomycin/therapeutic use , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Combined Modality Therapy , Etoposide/administration & dosage , Etoposide/therapeutic use , Humans , Male , Neoplasms, Germ Cell and Embryonal/pathology , Remission Induction , Testicular Neoplasms/pathology , Treatment Outcome
14.
J Chin Med Assoc ; 80(11): 705-711, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28919294

ABSTRACT

BACKGROUND: Our objective in this study was to evaluate the role and benefits in terms of local toxicity and biochemical disease-free survival (bDFS) following escalated-dose conformal radiation therapy in prostate adenocarcinoma. METHODS: The study population was composed of 53 patients with histologically proven T1b-T4, NO, MO prostate adenocarcinoma, having any Gleason score with prostate-specific antigen (PSA) of less than 50 ng/mL at diagnosis, given escalated dose EBRT (74 Gy) during the period between January 2011 and December 2013, retrospectively and evaluated for a period of 2 years post-radiation. Patients were followed up for a period of 2 years, beginning after completion of escalated dose external beam radiotherapy (EBRT) for biochemical failure as defined in ASTRO consensus committee guidelines 1996 and investigated for gastrointestinal, genitourinary skin toxicity. RESULTS: Out of 53 patients, 35 showed no biochemical failure at the end of 2 years following the completion of definitive escalated dose conformal radiotherapy while 18 were observed to have biochemical relapse. Acute gastrointestinal grade 1 toxicity was found in 26 patients, grade 2 in 24, and grade 3 only in 3 patients. Late gastrointestinal grade 0 toxicity was found in 16 patients, grade 1 in 28, grade 2 in 7 and grade 3 only in 2 patients. Grade 1 acute genitourinary toxicity was the highest in frequency observed in 28 of the total population followed by grade 2 in 21, grade 0 and grade 3 each, only in 2 patients. Late genitourinary Grade 0 toxicity was observed in 32 patients, grade 1 in 19, grade 2 and 3 only in 1 patient of the total population, respectively. CONCLUSION: Our data were comparable to international studies of dose escalation using 3D and beneficial as compared to conventional radiation therapy delivered by 2D in terms of biochemical failure rate and treatment related toxicity.


Subject(s)
Prostatic Neoplasms/radiotherapy , Radiotherapy, Conformal/methods , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prostate-Specific Antigen/analysis , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Radiotherapy Dosage , Radiotherapy, Conformal/adverse effects , Retrospective Studies
15.
J Coll Physicians Surg Pak ; 27(6): 342-347, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28689522

ABSTRACT

OBJECTIVE: To evaluate the efficacy of concurrent chemoradiation in patients with locally advanced inoperable squamous cell carcinoma of oral cavity in terms of local control and toxicity. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Institute of Nuclear Medicine and Oncology (INMOL), Lahore, from January 2008 to December 2013. METHODOLOGY: Sixty-nine patients with locally advanced inoperable oral cavity cancer, registered in INMOL hospital from January 2008 to December 2013 who fulfilled a pre-defined eligibility criteria, were enrolled in the study. Concurrent chemoradiation protocol consisted of conventional fractionation delivering 70 Gy with weekly Cisplatin (50 mg/m2) during the course of radiation. Tumor response was calculated by RECISTcriteria version 1.1 along with the median overall survival and disease-free survival. Acute treatment related toxicities were graded as (G). RESULTS: Thirty-six (52.17%) patients showed complete response; while 19 (27.54%), 8 (11.59%) and 6 (8.7%) were observed with partial response, stable and progressive disease, respectively. Treatment response was significant (p<0.001) in terms of responders vs. non responders to treatment. Median overall survival was 18.00 months; whereas, median disease-free survival remained 14.00 months. Main toxicities included mucositis (G3 and G4, 71%), xerostomia (G2 and G3, 82.5%), vomiting (G3 and G4, 51%), myelosuppression (G3 and G4, 26.2%), dermatitis (G3 and G4, 49.2%), and fatigue (G3 and G4, 57.9%). CONCLUSION: Platinum based CCR Tremained effective for inoperable oral cancer patients.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Chemoradiotherapy/adverse effects , Cisplatin/administration & dosage , Mouth Neoplasms/drug therapy , Mouth Neoplasms/radiotherapy , Radiation-Sensitizing Agents/administration & dosage , Adult , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cisplatin/toxicity , Combined Modality Therapy , Dose Fractionation, Radiation , Female , Humans , Male , Middle Aged , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Mucositis/chemically induced , Pakistan , Radiation-Sensitizing Agents/toxicity , Radiotherapy Dosage , Severity of Illness Index , Survival Rate , Treatment Outcome , Vomiting/chemically induced , Xerostomia/chemically induced
16.
Photodiagnosis Photodyn Ther ; 15: 94-9, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27238739

ABSTRACT

Conventional screening tools for ovarian cancer such as cancer antigen (CA-125) and trans-pelvic ultrasound have poor sensitivity and specificity, indicating the need for better and more reliable screening methodologies. Here, we investigate the capability of Raman spectroscopy as a screening technique for ovarian cancer. Raman spectra from the blood serum of healthy control and ovarian cancer subjects were measured. Highly significant Raman shifts (p<0.0001) and intensity variations were observed in the cancer group as compared to the healthy group. These spectral differences were exploited by support vector machine classifier towards computer assisted classification. Calculated evaluation metrics such as sensitivity (=90), specificity (=100), positive predictive value (=100) and negative predictive value (=87.5) for such classification indicated that these results are promising, with potential future application of Raman spectroscopy for ovarian cancer screening.


Subject(s)
Biomarkers, Tumor/blood , Diagnosis, Computer-Assisted/methods , Early Detection of Cancer/methods , Ovarian Neoplasms/blood , Ovarian Neoplasms/diagnosis , Spectrum Analysis, Raman/methods , Adult , Aged , Algorithms , Female , Humans , Male , Middle Aged , Pattern Recognition, Automated , Reproducibility of Results , Sensitivity and Specificity , Support Vector Machine
17.
Photodiagnosis Photodyn Ther ; 12(3): 459-65, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26073913

ABSTRACT

Increase in local temperature during light exposure of biological tissues plays an important role in determining the fate of most therapeutic modalities. Variations in the optical properties (absorption coefficient, scattering coefficient, anisotropy factor, optical depth etc.) of two cancer cell lines "Rhobdomyosarcoma and Cervical carcinoma" due to gradual increase in temperature were determine quantitatively with a double integrating sphere system. It was observed that all three coefficients showed decreasing tendency as the temperature increases for both the cell lines except for scattering coefficient of HeLa which remain constant within error limit. Anisotropy factor for both cell lines increased indicating temperature dependent subcellular density variations. Temperature dependent optical properties information may lead to precise dosimetry and could help clinicians for predicting the therapeutic modality outcome.


Subject(s)
Hot Temperature , Neoplasms/physiopathology , Optical Phenomena , Anisotropy , Cell Line, Tumor , Humans
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